Piotr Wiland

Publications of Piotr Wiland

• Access to biologic treatment for rheumatoid arthritis in Central and Eastern European (CEE) countries.

  Authors: Ewa Orlewska, Ioan Ancuta, Branimir Anic, Catalin Codrenau, Nemanja Damjanov, Predrag Djukic, Ruxandra Ionescu, Lubomir Marinchev, Evgeny L Nasonov, Tonu Peets, Sonja Praprotnik, Rasho Rashkov, Jana Skoupa, Witold Tlustochowicz, Malgorzata Tlustochowicz, Matija Tomsic, Tiina Veldi, Jelena Vojinovic, Piotr Wiland

  Medical science monitor : international medical journal of experimental and clinical research. 04/2011; 17(4):SR1-13.

  The aim of this study was to assess and compare patients' access to biologic anti-RA drugs in selected Central and Eastern European (CEE) countries and to analyze the determinants of differencesThe aim of this study was to assess and compare patients' access to biologic anti-RA drugs in selected Central and Eastern European (CEE) countries and to analyze the determinants of differences between countries. This is a multi-country survey study, based on a combination of desk research and direct contact with national RA stakeholders. Data was collected using a pre-defined questionnaire. Affordability was measured using an affordability index, calculated comparing the index of health care expenditures to the price index, using Poland as an index of 1. The percentage of patients on biologic treatment in 2009 was highest in Hungary (5% RA patients on biologic treatment), followed by Slovenia (4.5%), Slovakia (3.5%), Czech Republic (2.92%), Romania (2.2%), Estonia (1.8%), and Croatia, Serbia, Poland (below 1.5%). Infliximab, etanercept, adalimumab and rituximab were included in the reimbursement system in all countries, but abatacept and tocilizumab were included only in Slovakia. In Slovenia, public payer covered 75% of the price, and 25% is covered by supplementary health insurance; in Bulgaria public payer covered 50% of etanercept and adalimumab costs, and 75% of rituximab cost. In other countries, biologic drugs are reimbursed at 100%. Affordability index for biologic drugs was the lowest in Slovenia (0.4). In each country national guidelines define which patients are eligible for biologic treatment. Disease Activity Score (DAS28) of over 5.1 and failure of 2 or more disease-modifying anti-RA drugs, including methotrexate, are commonly used criteria. The most important factors limiting access to biologic anti-RA treatment in the CEE region are macroeconomic conditions and restrictive treatment guidelines.

• [The role of Th1, Th17, and Treg cells in the pathogenesis of rheumatoid arthritis including anti-inflammatory action of Th1 cytokines].

  Authors: Agata Kosmaczewska, Jerzy Swierkot, Lidia Ciszak, Piotr Wiland

  Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:397-403.

  Dysregulation in the immune system plays an important role in the pathogenesis of rheumatoid arthritis (RA). The persistent nature of arthritis strengthens the suggestion of immune dysfunction,Dysregulation in the immune system plays an important role in the pathogenesis of rheumatoid arthritis (RA). The persistent nature of arthritis strengthens the suggestion of immune dysfunction, consisting in predominance of the pro-inflammatory response. It seems that both local and systemic immune abnormalities, including PBMC secreting abnormal levels of pro- and anti-inflammatory cytokines, may be involved in the evolution of the disease. Helper T cells (Th) differentiate towards Th1, Th2, Th17, and Treg cells according to the cytokine microenvironment. Active RA results from the imbalance in distribution of functional pro-inflammatory Th17 and anti-inflammatory Treg cells. Affected Th1 cytokine secretion observed in the course of RA contributes to the increase in IL-17 production and Th17 infiltration in the synovial tissue. Current studies have demonstrated that pro-inflammatory Th1 cytokines may also exert an anti-inflammatory action on the balance between Th17 and Treg cells by promotion of Treg differentiation. In the paper, we also show the influence of TNF-alpha and its inhibitors on the distribution of Th subpopulations in RA patients.

• [Musculoskeletal symptoms in systemic lupus erythematosus and their differential diagnosis with rheumatoid arthritis].

  Authors: Piotr Wiland

  Annales Academiae Medicae Stetinensis. 01/2010; 56 Suppl 1:40-4.

  The musculoskeletal system is involved in nearly all patients with systemic lupus erythematosus (SLE). Transient arthralgias and arthritis are commonly observed. Some patients develop chronicThe musculoskeletal system is involved in nearly all patients with systemic lupus erythematosus (SLE). Transient arthralgias and arthritis are commonly observed. Some patients develop chronic synovitis, which can result in deformities of the joints known as Jaccoud's arthropathy and seen in 10-35% of patients with SLE. Many patients with SLE are initially misdiagnosed with rheumatoid arthritis (RA). Differentiation of SLE from RA can be done with diagnostic imaging, tests for anticitrullinated peptide antibodies (anti-CCP) and rheumatoid factor, and analysis of the clinical picture. It is important to undertake the differential diagnosis not only in early arthritis but also at later stages of the disease when new clinical symptoms have cast doubt on the diagnosis.

• [A case of early recognized Wegener's granulomatosis with renal involvement. Insights for early diagnosis].

  Authors: Agnieszka Matuszewska, Maria Misterska-Skóra, Piotr Wiland

  Annales Academiae Medicae Stetinensis. 01/2010; 56(1):41-4; discussion 44.

  Systemic necrotic and granulomatous vasculitis presents with vascular involvement in almost every organ, manifesting with stenosis, ischemia, infarction, or hemorrhage. The clinical picture dependsSystemic necrotic and granulomatous vasculitis presents with vascular involvement in almost every organ, manifesting with stenosis, ischemia, infarction, or hemorrhage. The clinical picture depends on the kind and size of the involved vessels and on the activity of the inflammatory process. Wegener's granulomatosis is a necrotic, granulomatous inflammation of small vessels of the upper and lower airways and kidneys. We present the case of a 25-year-old male in whom the definitive diagnosis of Wegener's granulomatosis was achieved within five weeks from onset. Among the first symptoms were microinfarcts localized in the fingertips and the nail matrix; their nature was investigated with capillaroscopy.

• [Active psoriatic arthritis during pregnancy: challenges and limitations of pharmacotherapy].

  Authors: Agnieszka Matuszewska, Maria Misterska-Skóra, Piotr Wiland

  Annales Academiae Medicae Stetinensis. 01/2010; 56 Suppl 1:45-7.

  Cases of psoriatic arthritis coexisting with pregnancy are sparse and therefore little is known about the fetal effect of medication in women with psoriatic arthritis. As a rule, drugs and dosagesCases of psoriatic arthritis coexisting with pregnancy are sparse and therefore little is known about the fetal effect of medication in women with psoriatic arthritis. As a rule, drugs and dosages are minimized in these patients. Among disease-modifying antirheumatic drugs, cyclosporine and sulphasalazine are preferred. Methotrexate and leflunomide are strictly contraindicated and must be withdrawn 3 months or 2 years, respectively, before a pregnancy is planned. Psoriatic arthritis may be treated during pregnancy with glucocorticosteroids, especially with prednisone or prednisolone. We present the case ofa 40-year-old gravida with psoriatic arthritis which exacerbated during the first trimester of pregnancy. Therapeutic implications in such cases are discussed.

• [Nodular changes in lungs in a patient with rheumatoid arthritis. Diagnostic and therapeutic difficulties. Case report].

  Authors: Ewa Krecipro-Nizińska, Ewa Morgiel, Helena Smiechowicz, Piotr Wiland

  Annales Academiae Medicae Stetinensis. 01/2010; 56 Suppl 1:86-90.

  Rheumatoid arthritis is a systemic inflammatory disease characterized by destructive synovitis and systemic extra-articular involvement exemplified by rheumatoid nodules occurring in the skin, lungs,Rheumatoid arthritis is a systemic inflammatory disease characterized by destructive synovitis and systemic extra-articular involvement exemplified by rheumatoid nodules occurring in the skin, lungs, and other parenchymatous organs. Antirheumatic drugs like methotrexate and leflunomide are known to predispose to the development of pulmonary rheumatoid nodules. We report the case of a 60-year-old male with rheumatoid arthritis previously treated with methotrexate and cyclosporin, in whom multiple pulmonary nodules were disclosed. The patient was extensively diagnosed to exclude any malignancy. Pulmonary rheumatoid nodules were recognized, methotrexate was withdrawn, and cyclophosphamide pulses were started. The size of the nodules decreased and the patient was started on cyclosporin.

• Does the KIR2DS5 gene protect from some human diseases?

  Authors: Izabela Nowak, Edyta Majorczyk, Andrzej Wiśniewski, Andrzej Pawlik, Maria Magott-Procelewska, Ewa Passowicz-Muszyńska, Jacek Malejczyk, Rafał Płoski, Sebastian Giebel, Ewa Barcz [......] Wioleta Łuszczek, Maciej Kurpisz, Marian Gryboś, Jacek Wilczyński, Piotr Wiland, David Senitzer, Ji-Yao Sun, Renata Jankowska, Marian Klinger, Piotr Kuśnierczyk

  PloS one. 01/2010; 5(8):e12381.

  KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation. In our studies onKIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation. In our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p=0.003, odds ratio [OR]=0.47, confidence interval [CI]=0.28-0.79), endometriosis (p=0.03, OR=0.25, CI = 0.07-0.82) and acute rejection of kidney graft (p=0.0056, OR=0.44, CI=0.24-0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p=0.0003, OR=0.35, CI=0.19-0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p=0.0017, OR=1.92, CI=1.28-2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p=0.005, OR=1.47, CI=1.13-1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p=0.017, OR=0.47, CI=0.25-0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p=0.0015, OR=2.13, CI=1.34-3.37). Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

• Rapid and complete resolution of ascites and hydrothorax due to nephrotic syndrome caused by renal amyloidosis in a patient with juvenile chronic arthritis treated with adalimumab.

  Authors: Beata Nowak, Sławomir Jeka, Piotr Wiland, Jacek Szechiński

  Joint, bone, spine : revue du rhumatisme. 03/2009;

• Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis.

  Authors: Bouke P C Hazenberg, Johan Bijzet, Pieter C Limburg, Martha Skinner, Philip N Hawkins, Irena Butrimiene, Avi Livneh, Olga Lesnyak, Evgeney L Nasonov, Anna Filipowicz-Sosnowska [......] Piotr Wiland, Huri Ozdogan, Peter D Gorevic, Hédi Ben Maïz, Merrill D Benson, Haner Direskeneli, Kalevi Kaarela, Denis Garceau, Wendy Hauck, Martin H van Rijswijk

  Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 07/2007; 14(2):133-40.

  OBJECTIVE: Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performanceOBJECTIVE: Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis. METHODS: Abdominal subcutaneous fat tissue of patients with AA amyloidosis was studied at the start of an international clinical trial with eprodisate (NC-503; 1,3-propanedisulfonate; Kiacta), an antiamyloid compound. All patients had renal findings, i.e. proteinuria (> or =1 g/day) or reduced creatinine clearance (20 - 60 ml/min). Controls were patients with other types of amyloidosis and arthritic patients without amyloidosis. Amyloid A protein was quantified by ELISA using monoclonal antihuman serum amyloid A antibodies. Congo red stained slides were scored by light microscopy in a semiquantitative way (0 to 4+). RESULTS: Ample fat tissue (>50 mg) was available for analysis in 154 of 183 patients with AA amyloidosis and in 354 controls. The sensitivity of amyloid A protein quantification for detection of AA amyloidosis (>11.6 ng/mg fat tissue) was 84% (95% CI: 77 - 89%) and specificity 99% (95% CI: 98 - 100%). Amyloid A protein quantification and semiquantitative Congo red scoring were concordant. Men had lower amyloid A protein values than women (p < 0.0001) and patients with familial Mediterranean fever had lower values than patients with arthritis (p < 0.001) or other inflammatory diseases (p < 0.01). CONCLUSIONS: Amyloid A protein quantification in fat tissue is a sensitive and specific method for detection of clinical AA amyloidosis. Advantages are independence from staining quality and observer experience, direct confirmation of amyloid AA type, and potential for quantitative monitoring of tissue amyloid over time.

• [Treatment outcome of spondyloarthropathy with infliximab]

  Authors: Agnieszka Głowska, Piotr Wiland, Jacek Szechiński

  Polskie archiwum medycyny wewnȩtrznej. 02/2005; 113(1):42-7.

  The spondyloarthropathies (SpA) are a heterogenous group of diseases associated with axial and peripheral arthritis, enthesitis, inflammatory bowel disorders, presence of HLA B27 antigen and oftenThe spondyloarthropathies (SpA) are a heterogenous group of diseases associated with axial and peripheral arthritis, enthesitis, inflammatory bowel disorders, presence of HLA B27 antigen and often with iridocyclitis. The aim of our study was to assess the efficacy of infliximab (chimeric monoclonal IgG 1 anti-TNF-alpha antibody) in the treatment of three patients with SpA. In two male patients (45- and 50-year old) psoriatic arthritis was diagnosed 28 and 22 years ago, and in 22-year old man ankylosing spondylitis was found before eight years. In all three cases dramatic response, almost complete resolution of joint manifestations and in patients with psoriatic arthritis regression of skin eruptions typical for psoriasis after one or two infusions was observed. In our opinion, the most optimal schedule of infliximab infusions was administration of the drug at weeks 0, 2, 6 and then every six weeks for at least 12 months. Discontinuation of therapy is associated with recurrence of symptoms of joint inflammation and increase in skin eruptions in patients with psoriatic arthritis within a few months.

• The prevalence of subclinical amyloidosis in Polish patients with rheumatoid arthritis.

  Authors: Piotr Wiland, Renata Wojtala, John Goodacre, Jacek Szechinski

  Clinical rheumatology. 06/2004; 23(3):193-8.

  The aims of this study were to determine the proportion of rheumatoid arthritis (RA) patients attending hospital in whom amyloid deposits were present in abdominal fat aspiration (AFA) samples, andThe aims of this study were to determine the proportion of rheumatoid arthritis (RA) patients attending hospital in whom amyloid deposits were present in abdominal fat aspiration (AFA) samples, and to assess possible risk factors for amyloid development in RA. One -hundred and twenty-one patients (16 males, 105 females) with RA referred to the Department of Rheumatology in Wroclaw between 1996 and 2001 were studied regardless of RA duration or laboratory findings. Abdominal subcutaneous fine-needle aspiration was performed, and samples of adipose tissue stained with alkaline Congo red then examined by polarized light microscopy. The presence or absence of amyloid fat deposits (AFD) was determined according to whether typical apple-green birefringence was observed. Amyloid deposits were found in 35 (29%) patients. Amyloidosis was significantly more common in males and in patients with longer disease duration. Patients with AFD had previously undergone less treatment with disease-modifying antirheumatic drugs (DMARDs) than those without AFD, and significantly fewer patients with AFD had previously taken methotrexate than those without AFD (25% vs 45%; p<0.01). Renal involvement was found in 12 of 35 patients with AFD (34%). Using the AFA technique, amyloid deposits were found commonly in RA patients, particularly in males with longer disease duration and in patients not treated intensively with DMARDs, especially methotrexate. AFA has potential useful application as a method for detecting amyloidosis before the overt occurrence of renal or other pathology related to amyloid deposits.

• [Renal tubular dysfunction in patients with rheumatoid arthritis starting with low dose of methotrexate]

  Authors: Piotr Wiland, Anna Wiela-Hojeńska, Jerzy Swierkot, Magdalena Hurkacz, Krystyna Orzechowska-Juzwenko, Jacek Szechiński

  Polskie archiwum medycyny wewnȩtrznej. 09/2003; 110(2):855-62.

  BACKGROUND: The elevation of N-acetyl-beta-D-glucosaminidase (NAG) in urine has been shown to be associated with reversible renal tubular damage. OBJECTIVES: The aim of the study was to examine theBACKGROUND: The elevation of N-acetyl-beta-D-glucosaminidase (NAG) in urine has been shown to be associated with reversible renal tubular damage. OBJECTIVES: The aim of the study was to examine the effect of first oral low dose methotrexate (MTX) on urinary excretion of NAG comparing with MTX concentration in serum and urine in a cohort of patients with rheumatoid arthritis (RA). METHODS: Urinary NAG to urinary creatinine ratio (NAG index) determined in 43 patients (5 males, 38 females) with RA who started taking the first oral dose of 10 mg of MTX. Urinary NAG index was observed at 24 h and 48 h after the first MTX dose. MTX concentration was measured in blood at 90 minutes and in blood and urine at 24 h after the drug administration. RESULTS: NAG-enzymuria was increased in 72.1% of the patients before administration of MTX therapy (10.8 UI/g creatinine). There was no change in NAG index at 24 and 48 h after first dose of MTX (9.1 and 10.7 UI/g of creatinine). No differences of NAG-enzymuria in non-steroidal anti-inflammatory drug (NSAID)-treated patients and NSAID-free patients before and after MTX administration were revealed. The patients with decreased creatinine clearance had before treatment higher NAG index than those with normal creatinine clearance but there was not any significant increase of NAG activity after first dose of MTX in the patients with decreased creatinine clearance. Continued treatment with MTX resulted in a decrease in NAG activity accompanied by serum C-reactive protein concentration. CONCLUSION: The use of low dose MTX with or without NSAIDs does not influence the renal tubular function in patients with RA.

• [Amyloidosis in the course of rheumatic disease: pathogenesis, incidence, clinical aspects and diagnosis]

  Authors: Piotr Wiland, Jacek Szechiński

  Polskie archiwum medycyny wewnȩtrznej. 08/2003; 110(1):789-96.

• [Treatment and prognosis of secondary amyloidosis in the course of rheumatic disease]

  Authors: Piotr Wiland, Jacek Szechiński

  Polskie archiwum medycyny wewnȩtrznej. 08/2003; 110(1):797-802.

• [Analysis of efficacy and safety of multiple intravenous infusion of anti-tumor necrosis factor-alpha monoclonal antibody (Remicade) combined with methotrexate compared with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis]

  Authors: Piotr Wiland, Agnieszka Głowska, Arkadiusz Chlebicki, Jacek Szechiński

  Polskie archiwum medycyny wewnȩtrznej. 12/2002; 108(5):1055-63.

  The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa (TNF-alfa) monoclonal antibody (Remicade)The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa (TNF-alfa) monoclonal antibody (Remicade) with methotrexate versus treatment with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis (RA). We investigate also the interval necessary to obtain the improvement in both treatment groups. 36 patients commencing intramuscular sodium aurothiomalate therapy with intramuscular depot methylprednisolone acetate at weeks 0, 4, 8 and 12 in addition to chrysotherapy were compared in retrospective analysis with 32 patients starting with multiple intravenous infusions of infliximab, anti-TNF-alfa monoclonal antibody (Remicade) and methotrexate at a stable dose. Patients were assessed by composite clinical score (DAS 28) and C-reactive protein during 22 weeks of therapy. At week 2 and 6 a significantly greater percentage of infliximab-treated than gold-treated RA patients achieved improvement in each clinical measurement of disease activity. At 22 week of treatment moderate and good response according to EULAR criteria was achieved in 91% of infliximab-treated patients and 58% gold treated patients (p < 0.001). Adverse events were more frequently observed in infliximab-treated patients, but only gold-treated patients discontinued treatment because adverse events (2 patients due to proteinuria, 2 patients due to mucocutaneous changes and one patient due to leucopenia). The higher percentage of adverse events in infliximab-treated patients was caused mainly by the occurrence of infusion reactions (23 reactions out of 160 infusions); most of them were mild (somnolentia and headache) and transient. Viral infections (including herpes simplex and zoster) were more common in patients treated with infliximab and methotrexate. Combination therapy of infliximab and methotrexate is more effective in reducing clinical and biochemical disease activity than gold with methylprednisolone treatment in RA patients during 22 weeks of treatment, especially in the first 6 weeks.

• High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment.

  Authors: Maria Ziolkowska, Mariola Kurowska, Anna Radzikowska, Grazyna Luszczykiewicz, Piotr Wiland, Wojciech Dziewczopolski, Anna Filipowicz-Sosnowska, Jacek Pazdur, Jacek Szechinski, Jacek Kowalczewski, Maria Rell-Bakalarska, Wlodzimierz Maslinski

  Arthritis and rheumatism. 08/2002; 46(7):1744-53.

  OBJECTIVE: To test the hypotheses that 1) proinflammatory cytokines affect osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa B ligand (sRANKL) production and therefore theOBJECTIVE: To test the hypotheses that 1) proinflammatory cytokines affect osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa B ligand (sRANKL) production and therefore the OPG and sRANKL levels differ in rheumatoid arthritis (RA) patients in comparison with healthy individuals; and 2) anti-tumor necrosis factor alpha (anti-TNF alpha) therapy influences OPG and sRANKL levels. METHODS: Sera were obtained from healthy individuals or RA patients receiving the combination of infliximab and methotrexate. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were isolated from RA patients. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissue obtained at total knee replacement in RA patients. Supernatants from cells stimulated with cytokines were collected after culture in vitro. Concentrations of OPG and sRANKL were determined by enzyme-linked immunosorbent assays. RESULTS: A strong positive correlation between OPG concentration and age was observed in healthy individuals but not in RA patients. The OPG and sRANKL levels were higher in RA patients than in healthy controls. Cultured FLS spontaneously secreted much higher amounts of OPG than PBMCs or SFMCs. Proinflammatory cytokines enhanced OPG production. Anti-TNF alpha treatment resulted in the normalization of serum OPG and sRANKL levels in RA patients without influencing the OPG:sRANKL ratio. CONCLUSION: Although higher serum levels of OPG and sRANKL are present in RA patients than in healthy individuals, the ratio of OPG:sRANKL is similar. There is an age-dependent increase of OPG but not sRANKL levels in healthy subjects. Anti-TNF alpha treatment results in the normalization of elevated levels of OPG and sRANKL in RA patients.

• Proximal tubule damage in patients treated with gentamicin or amikacin.

  Authors: Piotr Wiland, Jacek Szechciński

  Polish journal of pharmacology. 55(4):631-7.

  The present study aimed to determine the relationships between time of administration and dose of aminoglycosides, the extent of proximal tubule damage, evaluated by the urineThe present study aimed to determine the relationships between time of administration and dose of aminoglycosides, the extent of proximal tubule damage, evaluated by the urine N-acetyl-beta-D-glucosaminidase (NAG) activity, and to compare proximal tubule dysfunction in the patients treated with gentamicin and those receiving amikacin. The measurement of activity of NAG in urine was chosen to monitor of proximal tubule function. The studies were performed in 25 patients, who had to be administered gentamicin or amikacin by intramuscular injections. In both groups, the maximum NAG activities in urine were detected most frequently after the 7th day of the therapy. A significant difference in NAG activities in urine was noted between the values observed in the course of treatment with aminoglycosides and those determined before start of the treatment. NAG activity in urine significantly decreased following discontinuation of aminoglycoside antibiotic administration. The activities did not decrease quite to the pretreatment level but the remaining difference proved to be insignificant. In the course of aminoglycoside treatment, 7 patients demonstrated an increase in serum creatinine levels exceeding 0.4 mg%. It should be stressed that no pronounced differences in nephrotoxicity and, in particular, in their potential to induce injury to the proximal tubule have been disclosed between gentamicin and amikacin. Their significant, damaging effect on integrity of proximal tubule was demonstrated, which was evidenced by the clear increase in urinary NAG activity during administration of either drug. Nevertheless, only in a small fraction of such cases (12-16%), the increase promoted development of renal insufficiency, usually of a transient character. Monitoring of the increase in urinary NAG activities in line with observations on creatinine levels permits to distinguish a subgroup of patients who may be suspected of development of overt nephrotoxicity. In such cases cessation of aminoglycoside administration is required.