The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study.

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen-positive [HBsAg(+)] donors to HBsAg(-) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow-up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti-HBs) levels. The present retrospective, longitudinal study (clinicaltrial.gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL undergoing KT from HBsAg(+) donors (n = 43) and HBsAg(-) donors (n = 86). During the median follow-up duration of 58.2 months (range 16.7-158.3 months), there were no significant differences in graft and patient survivals. No HBV-infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(+) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV-associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(+) donors with no HBV prophylaxis (n = 20) provided comparable outcomes with those treated with lamivudine alone (n = 21) or lamivudine in combination with HBV immunoglobulin (n = 2). In conclusion, KT without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia to HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.

Glutaraldehyde erythropoietin protects kidney in ischaemia/reperfusion injury without increasing red blood cell production.

BACKGROUND AND PURPOSE: Recombinant human erythropoietin (rHuEPO) is currently the mainstay of renal anaemia treatment. Recently, rHuEPO has been shown to provide pleiotrophic tissue protection in various pathological conditions. However, the benefits of rHuEPO beyond anaemia treatment are limited because it increases red blood cell mass. Carbamylated erythropoietin (CEPO) is the first rHuEPO derivative that lacks erythropoietic activity but retains tissue protection properties. Since carbamylation targets lysine residues on rHuEPo, we hypothesized that targeted lysine modifications of rHuEPO may result in a novel non-erythropoietic erythropoietin. EXPERIMENTAL APPROACH: rHuEPO was subjected to various targeted lysine modifications. In vitro cytoprotection and apoptosis were evaluated using P19 and HEK293 cells. In vivo erythropoiesis was performed by administering the derivatives to animals for 2 weeks. Renoprotection was tested on an ischaemia/reperfusion (I/R) model. KEY RESULTS: We synthesized a novel derivative, a glutaraldehyde erythropoietin (GEPO). This construct abolished in vivo erythropoiesis. Biochemical characterization showed that GEPO was more electrostatically negative than rHuEPO. Immunoprecipitation experiments revealed that GEPO bound to the IL3RB/EPOR heterotrimeric receptor and ameliorated cellular apoptosis via the activation of Bcl-2. Notably, Bcl-2 activation was suppressed by the JAK2 inhibitor, tyrphostin AG490. In vivo experiments showed that GEPO also ameliorated kidney damage due to I/R injury both functionally and histologically. CONCLUSIONS AND IMPLICATIONS: Herein, we describe a novel lysine-modified rHuEPO, glutaradehyde-EPO (GEPO), obtained from a simple reaction. This derivative has no erythropoietic properties but retains cell-protective characteristics both in vitro and in vivo, with promise for future use as an adjunctive treatment of kidney disease.

Angiotensin II receptor blocker partially ameliorated intrarenal hypoxia in chronic kidney disease patients: a pre-/post-study.

Chronic intrarenal hypoxia has been regarded as a pathogenic factor of progressive renal damage. However, the lack of available human data has impeded the progress in this field. In this work, blood oxygen level-dependent magnetic resonance imaging was used to determine intrarenal oxygen status pre- and post-angiotensin receptor blockade (olmesartan) treatment in normal subjects, diabetic chronic kidney disease (CKD) patients and non-diabetic CKD patients. The mean R2*, which represents intrarenal oxygenation, was significantly lower in the control group than in the CKD group (12.42 ± 0.53 /s vs 18.89 ± 3.15 /s, P < 0.01), indicating the presence of intrarenal hypoxia in the CKD patients. The olmesartan treatment induced a 16.2 ± 7.7% decrement of the mean R2* in CKD patients, suggesting that this drug had an intrarenal hypoxia ameliorating effect.

Endothelial progenitor cells in Asian kidney transplant patients.

BACKGROUND: Endothelial progenitor cells (EPC) involved in endothelial repair and maintenance are restored following renal transplantation. There are scarce data regarding EPC in Asian kidney allograft patients. AIM: We determined the EPC numbers in Thai renal allograft patients to compare with various other parameters. PATIENTS AND METHODS: The EPC numbers which were verified as CD 133+/VEGFR-2 cells in peripheral blood of 38 renal transplant recipients were measured by flow cytometry, and by a cell culture assay using acetylated low-density lipoprotein and Ulex europaeus agglutinin-1 immunofluorescence. Renal function calculated as estimated glomerular filtration rate (eGFR) was obtained by the abbreviated Modification of Diet in Renal Disease (MDRD) formula. RESULTS: Renal allograft patients had lower EPC numbers than normal controls (P < .05). The EPC numbers showed a significant correlation with renal allograft function (P < .05). Recipients with stable eGFR at 12 months of follow-up displayed significantly greater EPC numbers at baseline compared with those subjects who experienced a decline in eGFR (P < .05). Recipients using angiotensin receptor blockers had greater EPC numbers at baseline and better 12-month renal allograft function (P < .05). CONCLUSION: EPC numbers may influence the fate of renal allograft function. Enhancing EPC numbers may be a new strategy to improve long term renal allograft function.

A prevalence of posttransplantation cancers compared with cancers in people with human immunodeficiency virus/acquired immunodeficiency syndrome after highly active antiretroviral therapy.

BACKGROUND: Organ transplant recipients and human immunodeficiency virus & acquired Immunodeficiency Syndrome (HIV/AIDS) patients have immune deficiencies that are possible mechanisms to develop malignancy. The type of cancers associated with these 2 conditions might elucidate this premise. AIM: Our aim was to compare prevalence and type of cancers between kidney transplant recipients and patients with HIV/AIDS. PATIENTS AND METHODS: We retrospectively reviewed 344 patients who underwent kidney transplantation from 1973 to 2007 compared them with 863 subjects with HIV/AIDS at the HIV-Netherlands/Australia/Thailand Research Collaboration (HIV-NAT) from 1997 to 2007. AIDS-defining cancers were excluded from the analysis. We compared the relative tumor risk with the age- and gender- matched general population of metropolitan Bangkok. RESULTS: The overall cancer risk for kidney transplant recipients (standardized incidence ratio [SIR] = 4.21) was comparable with HIV-infected patients (SIR = 3.88). Uroepithelial cancer was the most prevalent type in kidney transplant recipients, whereas cervical cancer was the most common malignancy in HIV-infected patients. The risks of developing hepatoma and non-Hodgkin's lymphoma were comparable between the groups. CONCLUSION: Kidney transplant recipients and HIV-infected patients show increased overall risks of certain types of cancers.

De novo sirolimus-based regimen in Thai renal transplant recipients.

BACKGROUND: Calcineurin inhibitor (CNI) toxicity is a common cause of chronic allograft nephropathy. Although de novo sirolimus (SRL) with CNI minimization may provide better graft function, studies in Asian recipients are lacking. AIM: We sought to determine the 1-year outcomes of renal transplant patients who received a de novo SRL-based regimen with CNI minimization. PATIENTS AND METHODS: A single-center, prospective study of de novo SRL-based, reduced-dose cyclosporine regimen was performed from 2004 to 2007. The control group was a historical cohort of a cyclosporine-based regimen (cyclosporine, prednisolone, and mycophenolate mofetil). The 1-year outcome parameters included renal function, rate of acute rejection, biopsy-proven CNI toxicity, graft and patient survivals. RESULTS: The SRL-based regimen achieved 100% 1-year graft and patient survivals. The renal function was comparable between the SRL-based and CNI-based regimens (serum creatinine 1.32 +/- 0.45 and 1.45 +/- 0.43 mg/dL; P = .27). The rate of biopsy-proven acute rejection was comparable (9.5% and 13%; P = .68). The SRL-based regimen had a higher rate of biopsy-proven CNI toxicity (28.5% and 9.7%; P = .03). CONCLUSIONS: De novo SRL-based regimen with CNI minimization provides excellent transplant outcomes. The strategy to minimize or withdraw CNIs may achieve excellent graft function. A prospective study targeting lower CNI trough levels in Asian transplant recipients is required.

Efficacy of enteric-coated mycophenolate sodium in patients with resistant-type lupus nephritis: a prospective study.

The role of mycophenolate mofetil (MMF) is still controversial in the treatment of cyclophosphamide-resistant proliferative lupus nephritis (PLN). Enteric-coated mycophenolate sodium (EC-MPS) has less gastrointestinal adverse effects than MMF and is, therefore, increasingly utilised in organ transplantation. The aim of this study was to compare the efficacy and safety of EC-MPS versus an extended-course of intravenous cyclophosphamide (ED-IVCY) in resistant-type PLN. Thirty-one, biopsy-proven PLN, patients who failed to respond to an induction of IVCY were enrolled in a prospective, open-labelled, historically controlled study. Patients received 6 month of EC-MPS (720 mg b.i.d.) treatment. The patients in the ED-IVCY group, collected from a database, received a repeated 6-month course of monthly IVCY 0.5-1 g/m(2) of body surface area. Both groups received 0.5-1 mg/kg/day of prednisolone. Primary outcomes were partial or complete responses. A repeated kidney biopsy was performed to evaluate the histological response. No serious adverse events or patient deaths were observed during the study. Both groups had comparable baseline characteristics. At 6 months, the EC-MPS group had a comparable response rate with the ED-IVCY group. There were significantly less adverse events in the EC-MPS group. Repeated biopsies showed significant improvement in the EC-MPS group. EC-MPS provides salutary efficacy and safety in the treatment of resistant-type PLN and can be a suitably alternative treatment to ED-IVCY.

A novel simple hemoglobin dilution technique to measure hemodialysis vascular access flow.

Measurement of the vascular access flow rate (Q(a)) is a widely accepted method for surveillance and predicting access failure. Among current practical methods, the ultrasound dilution technique is standard, but this requires a costly device available in few hemodialysis (HD) centers. Here, we devised a simple hemoglobin dilution technique to accurately measure Q(a) without the need for any special machines. Before HD, values of Q(a) were determined in each of 30 patients by hemoglobin dilution and then, in the same session, by ultrasound dilution. There was a significant correlation between the two techniques using automated hemoglobin and hematocrit or centrifuge-measured hematocrit levels to calculate HD fluid-derived Q(a) values. Our study shows that the HD dilution technique, using no special device, is economical, highly accurate, and easy to perform, and can be used as an alternative to standard ultrasound dilution for vascular access surveillance.

Antioxidative effects of erythropoietin.

Erythropoietin (EPO) has been shown to exert cytoprotective effects on erythroid progenitor cells as well as various non-erythroid cells. Experimental studies have demonstrated the renoprotective effects of EPO in various acute and chronic renal injury models. These protective effects have been largely attributed to antiapoptotic signalings of EPO. However, injured cells undergoing apoptosis are generally too severely damaged to function properly. Therefore, simply corrupting apoptotic pathway is unlikely to be an effective strategy, because the remaining damaged cells may not function appropriately, or they may eventually undergo necrotic cell death. Recent evidences suggest that EPO also provides cytoprotection by ameliorating oxidative stress, the principal cellular insult. EPO may exert its antioxidative effects directly by exploiting intracellular antioxidative mechanisms such as heme oxygenase-1 and glutathione peroxidase. In addition, EPO may act indirectly by inducing iron depletion and thereby inhibiting iron-dependent oxidative injury. Increasing red blood cells by EPO may also indirectly reduce cellular oxidative stress, as red blood cells are loaded with a substantial amount of antioxidative enzymes. Further investigation regarding the mechanisms of cellular antioxidative responses to EPO would provide a better insight to cytoprotective action of EPO, and would support the development of better cytoprotective drugs in the near future.

Comparison of middle-molecule clearance between convective control double high-flux hemodiafiltration and on-line hemodiafiltration.

Hemodiafiltration (HDF) is now a well-recognized treatment modality for end-stage renal disease (ESRD) patients. It provides superior characteristics over conventional hemodialysis in many respects. On-line HDF, however, which has been mainly used in clinical practice, requires a special machine. Interestingly, the recently innovated convective-control double high-flux hemodiafiltration (CC-DHF) machine can provide HDF treatment with an adjustable convection rate by using the conventional volume-controlled dialysate flow hemodialysis machine in a modified way. The present study was conducted to compare the efficacy of CC-DHF compared to on-line HDF in terms of middle and small solute clearances in 12 stable, chronic hemodialysis patients who underwent hemodialysis three times a week for at least 6 months. The results showed that the beta 2-microglobulin (beta 2M) removal represented by the beta 2M clearance in CC-DHF was comparable to that in on-line HDF (112.4+/-17.0 vs. 119.4+/-15.5 ml/min respectively, NS). Also, the beta 2M reduction ratio in the CC-DHF group did not differ from the on-line HDF group (85.5+/-4.2% vs. 86.1+/-6.7%, NS). With regard to small solute clearances, the values of single-pool Kt/V and phosphate clearance did not differ between CC-DHF and on-line HDF groups. In conclusion, CC-DHF provides removal of beta 2M and small molecule uremic toxins that is comparable to on-line HDF. An on-line HDF machine may not be available in all hemodialysis centers, whereas CC-DHF can be easily set up, with proper precautions regarding the fluid quality. Therefore, CC-DHF can provide the benefits of convective therapy to patients in situations where use of an on-line HDF machine is limited.

Correlations between antinucleosome antibodies and anti-double-stranded DNA antibodies, C3, C4, and clinical activity in lupus patients.

OBJECTIVE: To examine the correlations between antinucleosome antibodies and anti-double-stranded (ds) DNA antibodies, complement (C) 3 and 4 levels, and clinical activities in SLE patients. METHODS: Antinucleosome antibodies and anti-dsDNA antibodies were detected by enzyme-linked immunosorbent assays (ELISA). The levels of C3 and C4 were measured by nephelometry. Clinical activities were determined by SLE Disease Activity Index (SLEDAI). RESULTS: Of 65 SLE patients, the prevalence of antinucleosome antibodies were higher than anti-ds DNA antibodies (52.3 vs 36.9%, respectively, p < 0.05). Similar results were obtained in 45 active SLE patients, 64.4% for antinucleosome antibodies and 46.7% for anti-ds DNA antibodies. Of 34 patients lacking anti-ds DNA antibodies, 16 (47.1%) were shown antinucleosome antibodies. Activity of antinucleosome antibodies was significantly correlated with the SLEDAI scores and inversedly correlated with the C3 levels but not with the C4 levels. CONCLUSION: Antinucleosome antibodies could be one of the earliest and most sensitive markers in diagnosis of SLE, particularly in anti-dsDNA antibodies-negative patients. More importantly, antinucleosome antibodies is correlated with clinical activities and C3 levels.

Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis.

Noninvasive molecular tests of urine cells have been developed to monitor the activity of kidney diseases. We evaluate whether measurement of urinary messenger RNA (mRNA) levels of chemokine and growth factor genes could distinguish between diffuse proliferative lupus nephritis (class IV LN) and others and whether it is able to predict the response to therapy. Prebiopsy urine samples were collected from 26 LN patients. Urine specimens were serially collected over a period of 6 months from class IV LN patients who were receiving standard immunosuppressive treatments. Urinary interferon-producing protein 10 and its CXC chemokine receptor (CXCR)3, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF) mRNA levels were analyzed by quantitative real-time polymerase chain reactions. Levels of chemokine or growth factor mRNAs in urine could distinguish class IV LN from others, with a sensitivity of 85% and a specificity of 94%. The receiver-operative characteristic curve demonstrated that urine mRNA levels of these genes could identify active class IV LN with an accuracy greater than the current available clinical markers, namely systemic lupus erythematosus (SLE) disease activity index, proteinuria, renal function, or urinalysis. A significant reduction of interferon-producing protein 10 (IP-10), CXCR3, TGF-beta, and VEGF mRNA levels from baselines was observed in patients who responded to therapy, whereas the levels tended to increase in those who resisted to treatment. Measurement of urinary chemokine and growth factor mRNAs can precisely distinguish class IV LN from others. Temporal association between these markers and therapeutic response is demonstrated. This noninvasive approach serves as a practical tool in diagnosis and management of LN.

Convective-controlled double high flux hemodiafiltration: a novel blood purification modality.

Convective-controlled double high flux hemodiafiltration (CC-DHF) was set-up using two high flux dialyzers. The convection occurred in the first while the fluid replacement took place in the second dialyzer. The system of CC-DHF basically resembled that of hemodiafiltration. CC-DHF was performed in 9 chronic hemodialysis Thai patients who had been treated with high flux hemodialysis for at least 6 months. When compared with high flux hemodialysis, CC-DHF could provide higher Kt/Vurea (2.4+/-0.4 vs. 2.0+/-0.4, p<0.05) and beta2-microglobulin clearance (106.2+/-15.4 vs. 48.9+/-6.1 ml/min, p<0.01). Following 6-month therapy of CC-HDF, the predialysis beta2-microglobulin levels were reduced by 12.7% while the values of Kt/Vurea were consistently higher than 2.7. The quality of life consistently improved during the 6 months of CC-DHF treatment. There were no differences in clinical and technical complications between CC-DHF and high flux hemodialysis. In conclusion, CC-DHF could provide performance comparable to hemodiafiltration without the need for expensive hemodiafiltration machines.

Monitoring of T-cell subsets in patients treated with anti-CD 25 antibody.

Daclizumab and basiliximab, the antibodies to the interleukin-2 receptor (anti-IL-2R), decrease the incidence of acute rejection in renal transplantation. However, prolonged blockade of IL-2 receptor (IL-2R:CD25) may hamper apoptosis of reactive T-cell clones and thus may obstruct tolerance induction. We determined the effect of varying doses of anti-IL-2R on the number of CD3+CD25+ cells as an index of CD 25 blockade. The number of CD3+CD25+ cells was determined in four groups of induction therapies: no antibody induction; two doses of 50 or 25 mg daclizumab on day 0 and day 14; and two doses of 20 mg basiliximab at day 0 and day 4 (n=10, 24, 10, and 10, respectively). The number of CD3+CD25+ cells were monitored in whole blood before antibody infusion as well as 24 hours thereafter and weekly after transplantation. With two doses of 50 mg daclizumab, two doses of 25 mg daclizumab, and two doses of 20 mg basiliximab, the expression of CD3+CD25+ cells was completely suppressed for 12, 10, and 12 weeks posttransplantation, respectively. The reappearance of CD3+CD25+ cells above the baseline for each induction regimen was: 17 weeks for two doses of 50 mg daclizumab, 11 weeks for two doses of 25 mg daclizumab, and 13 weeks for two doses of 20 mg basiliximab. Monitoring of CD3+CD25+ cells may be utilized to tailor anti-IL-2R administration at a minimal dosage, yet retaining adequate IL-2R blockade for at least 3 months posttransplantation.

Life-long food restriction prevents renal membrane lipid deposition and lowers renal work in rats.

Renal cortical brush-border (BBM), basolateral membrane (BLM), and medullary plasma membrane (mPM) preparations were analyzed to assess the effects of life-long food restriction in aged rats on membrane lipid content. Young male Fischer 344 x Brown-Norway F1 rats consumed food ad libitum (young AL) or were food-restricted (FR, 60% of AL consumption) for either 6 weeks (young FR) or until the age of 30 months old (old FR). Senescent FR rats had 50 per cent decreases in fractional excretion of Na and K (p < 0.001) as compared with the young AL rats. Long-term FR reduced phosphate and titratable acid excretion by 80 per cent (p < 0.001). These values were not significantly different from those observed in young rats during 6 weeks of FR. Food restriction decreased renal Na, K-ATPase activity by 50 per cent (p < 0.001) in both old and young FR animals. Reduction of food intake, in old and young rats, decreased all BBM phospholipid concentrations (phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin) by 50 per cent than in the AL rats (p < 0.001). In BLM, chronic FR resulted only in lower phosphatidylcholine concentration (by 21%, p < 0.05) while phosphatidylethanolamine was increased approximately 80 per cent (p < 0.001). Total phospholipid content in mPM was progressively decreased by 23 per cent (p < 0.05) in the young FR group to be 55 per cent (p < 0.001) in the old FR rats. Cholesterol content was reduced in BBM and mPM by 38 per cent and 25 per cent (p < 0.05), respectively, during long-term FR. Both total phospholipid and cholesterol contents detected in mPM of the old FR rats were significantly lower than those obtained from the young FR animals (by 42%, p < 0.001 and 12%, p < 0.05, respectively). Plasma glucose, blood urea nitrogen, and body weight maintained at significantly lower levels during chronic FR. That life-long FR could prevent renal membrane lipid deposition and could lower renal work may explain the mechanisms that FR can delay the onset and diminish the severity of age-associated renal diseases.

Necrotizing ileitis caused by cytomegalovirus in patient with systemic lupus erythematosus: case report.

We report a systemic lupus erythematosus (SLE) patient with necrotizing ileitis diagnosed at a tertially care centre in Thailand. The patient was surgically explored because peritonitis was suspected and segmental gangrenous and perforation of the terminal iliem were found. The pathological finding was necrotizing ileitis with appearance of cytomegalic intranuclear inclusion body. The presence of cytomegalovirus (CMV) infection in tissue was confirmed by CMV-DNA detection using polymerase chain reaction and ELISA probe hybridization method. The hemoculture and peritoneal fluid culture results revealed no pathogenic organisms. Postoperatively, the clinical course of the patient deteriorated and she developed hypotension. Vasopressive drugs were administered without clinical improvement. She expired on day 5 postoperation. Regarding CMV infection, the organism involves the small bowel in only 4.3 per cent of all CMV infections of the gastrointestinal tract. Isolated cases of ileal perforation due to CMV infection have never been reported in a SLE patient. Thus, chronic right lower abdominal pain, fever with or without diarrhea in immunocompromised patients should cause clinicians to consider CMV ileitis in the differential diagnosis. Immediate surgical resection and prompt antiviral therapy lead to successful treatment.

Exchange transfusion in severe falciparum malaria: a simple method modified from hemodialysis circuit.

We set up a simple extracorporeal circuit, modified from the extracorporeal method generally used in conventional hemodialysis, for exchange transfusion. Temporary vascular access was used in exchange transfusion for both draining the infected blood and infusion of the freshly non-infected blood. This method of exchange transfusion was performed in 3 severe complicated falciparum malaria patients who had a percentage of parasitemia of 80, 40, and 35. The magnitude of parasitemia decreased immediately to less than one per cent and this value persisted twenty-four hours after the procedure. No complications of exchange transfusion were detected in all patients. Erythrocyte morphology determined by scanning electron microscopy was unaltered by exchange transfusion. Because of the simplicity, the effectiveness, and the safety of the procedure, this extracorporeal circuit modified from hemodialysis circuit would be a more beneficial exchange transfusion method in the treatment of severe complicated falciparum malaria than the manually-performed one.

Pharmacokinetics of intraperitoneal cefazolin and gentamicin in empiric therapy of peritonitis in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate cefazolin and gentamicin in Thai continuous ambulatory peritoneal dialysis (CAPD) patients treated following the International Society for Peritoneal Dialysis (ISPD) 1996 recommendations for the empiric therapy of CAPD-related peritonitis. DESIGN: Prospective and descriptive study. SETTING: Institutional level of clinical care. PATIENTS: CAPD-related peritonitis patients were diagnosed by dialysate effluent white cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50%. There were 18 patients, all at least 15 years of age, entered; all completed the study. INTERVENTION: In accordance with the ISPD 1996 recommendations, the antibiotic regimen included continuous intraperitoneal (IP) cefazolin and once-daily IP aminoglycoside. Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate, respectively. Gentamicin, 0.6 mg/kg body weight, was given IP once daily. Duration of treatment was 120 hours. MAIN OUTCOME MEASURES: Serum and dialysate effluent samples of the 18 CAPD patients with peritonitis were measured and used for the synthesis of pharmacokinetic equations that could predict drug concentrations at any treatment time. RESULTS: Following administration according to the ISPD 1996 treatment recommendations, serum cefazolin reached levels higher than the recommended levels (8 microg/mL) at 3.3 minutes after drug administration, and persisted through the 5-day duration of the study. Dialysate cefazolin levels during the studied period also were persistently higher than the recommended values. The peak serum gentamicin levels were lower than the suggested values of 4 microg/mL, whereas the trough serum gentamicin levels were higher than the minimal toxic concentrations (2 microg/mL). Dialysate gentamicin levels were higher than therapeutic concentrations for only 4.75 hours in each day. It was difficult, using pharmacokinetic studies, to adjust the dosage regimen of gentamicin to achieve appropriately therapeutic levels in both serum and dialysate. CONCLUSIONS: The ISPD 1996 recommended dosage of continuous IP cefazolin could be appropriate for the treatment of CAPD-related peritonitis. Once-daily IP gentamicin administration, however, has less therapeutic benefit and should be re-evaluated.