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1.
Clin Hemorheol Microcirc ; 69(1-2): 69-75, 2018.
Article in English | MEDLINE | ID: mdl-29630539

ABSTRACT

BACKGROUND: Renal transplant patients have a higher risk for malignancies of the renal transplant. In most cases suspected renal malignancies will be detected during the regular ultrasound follow-up and will require cross-sectional imaging to rule out a malignant aetiology. But it is well known that contrast agents for computed tomography or magnetic resonance imaging are critical in patients with limited renal function. OBJECTIVE: This study aims to compare the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) and gold standard imaging modalities in characterizing suspected renal transplant malignancies in renal transplant patients. METHODS: A total of 22 renal transplant patients who underwent one or more CEUS examinations and at least one standard imaging modality (CT or MRI) between 2005 and 2017 were included. Patient ages ranged from 28.2 years to 74.6 (mean age 55.7 years; SD±13.0 years). CEUS of 22 patients was correlated with a standard imaging modality, CT (15 out of 22) or MRI (7 out of 22), serving as gold standard. RESULTS: CEUS showed a sensitivity of 100%, a specificity of 94.4%, a positive predictive value (PPV) of 80%, and a negative predictive value (NPV) of 100%. CONCLUSIONS: CEUS is an eligible method to help characterizing suspected renal malignancies in renal transplant patients compared to the well-established imaging modalities CT and MRI. As an imaging modality with no nephrotoxic effects CEUS can be used repeatedly even in patients with limited renal function.


Subject(s)
Contrast Media/therapeutic use , Kidney Neoplasms/diagnostic imaging , Kidney Transplantation/adverse effects , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Ultrasonography/methods , Adult , Aged , Female , Humans , Kidney Neoplasms/pathology , Male , Middle Aged
2.
Clin Hemorheol Microcirc ; 69(1-2): 77-82, 2018.
Article in English | MEDLINE | ID: mdl-29630540

ABSTRACT

BACKGROUND: Despite of the more potent immunosuppressive medication, vascular rejection is still a major issue after renal transplantation. Renal biopsy is the gold standard diagnostic to evaluate acute and chronic allograft rejection. As it is an invasive diagnostic there is the risk of complications like haematoma, arteriovenous fistulas, active bleeding or infection. Contrast-enhanced ultrasound is a non-invasive imaging modality that allows visualising renal transplant perfusion. OBJECTIVE: To analyse the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) compared to biopsy as gold standard in diagnosing vascular rejection in renal transplant patients. METHODS: A total of 57 renal transplant recipients with poor renal allograft function with initial diagnostic imaging between 2006 and 2017 were included in the study. Clinical data and imaging studies were analysed retrospectively. The diagnostic accuracy of CEUS in diagnosing vascular rejection of the renal transplant was compared to renal biopsy as gold standard. Out of 57 patients 7 patients showed signs of vascular rejection in biopsy. In 6 out of these 7 patients CEUS described irregularities in renal perfusion suspicious of vascular rejection. RESULTS: CEUS showed a sensitivity of 85.7%, a specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 98.0%. CONCLUSIONS: CEUS is a safe, non-nephrotoxic imaging modality for the initial imaging of renal transplant recipients with elevated kidney function parameters suspicious of vascular rejection. Compared to renal biopsy as gold standard CEUS shows a high specificity and PPV in detecting signs of vascular rejection. Since sub-types of vascular rejection with cellular and humoral components with greater risk for allograft loss have been described renal biopsy is inevitable in these cases.


Subject(s)
Contrast Media/therapeutic use , Graft Rejection/diagnostic imaging , Kidney Transplantation/adverse effects , Kidney/pathology , Ultrasonography/methods , Adult , Aged , Female , Humans , Kidney Transplantation/methods , Male , Middle Aged , Retrospective Studies , Young Adult
3.
Clin Hemorheol Microcirc ; 67(3-4): 407-413, 2017.
Article in English | MEDLINE | ID: mdl-28885208

ABSTRACT

BACKGROUND: Vascular complications in renal transplant patients are a well-known issue in post transplant patient care. If malfunctioning of the renal transplant is suspected to be caused by vascular complications an early diagnosis and therapy is required to maintain the renal transplant. Computed tomography (CT), digital substraction angiography (DSA) and radioisotope renography are the gold standard imaging modalities to diagnose vascular complications. OBJECTIVE: To analyse the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) in comparison to the standard imaging modalities CT, DSA and radioisotope renography in the diagnosis of vascular complications in renal transplant patients. METHODS: A total of 33 renal transplant recipients with elevated kidney function parameters with initial diagnostic imaging between 2006 and 2017 were included in the study. The imaging studies and clinical data were analysed retrospectively. The diagnostic accuracy of CEUS was compared to CT, DSA and renal scintigraphy respectively which are classified as gold standard for diagnosis of vascular complications in renal transplant patients. Out of 23 patients 15 patients showed vascular complications in CT, DSA or radioisotope renography and in 15 out of 15 patients CEUS detected the vascular complication. RESULTS: CEUS showed a sensitivity of 100%, a specificity of 66.7%, a positive predictive value (PPV) of 71.4%, and a negative predictive value (NPV) of 100%. CONCLUSIONS: CEUS is a non-nephrotoxic and safe method for the initial imaging of vascular complications in renal transplant recipients. Compared to the gold standard imaging modalities CT, DSA and radioisotope renography CEUS shows a high sensitivity and NPV in detecting vascular complications. In cases with suspected stenosis of the transplant renal artery additional DSA might be needed.


Subject(s)
Contrast Media/therapeutic use , Kidney Transplantation/adverse effects , Kidney/pathology , Ultrasonography/methods , Adult , Aged , Female , Humans , Kidney Transplantation/methods , Male , Middle Aged , Young Adult
4.
Scand J Immunol ; 82(2): 102-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25970072

ABSTRACT

The rejection process remains the key unsolved issue after transplantation of disparate tissue. The CC chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) has been reported to be involved in the process of alloimmune interaction. Spiegelmers are l-oligonucleotides that can be designed to bind to pharmacologically relevant target molecules. Here, we tested a high-affinity Spiegelmer-based MCP-1 inhibitor (mNOX-E36) in an allogeneic heart transplant model. Fully vascularized allogeneic heterotopic heart transplantations from BALB/c to C57BL/6 mice were performed. Mice were either treated with the anti-MCP-1-Spiegelmer (mNOX-E36) in monotherapy or in combination with subtherapeutic doses of cyclosporine A (CsA) (10 mg/kgBW/day) for 10 days. Controls received equivalent doses of a non-functional Spiegelmer (revmNOX-E36). Graft survival of allogeneic heart transplants was slightly but significantly prolonged under mNOX-E36 monotherapy (median graft survival 10 day ± 0.7) compared to revmNOX-E36 (median graft survival 7 day ± 0.3; P = 0.001). A synergistic beneficial effect could be seen when mNOX-E36 was administered in combination with subtherapeutic doses of CsA (18 day ± 2.8 versus 7 day ± 0.3; P < 0.0001). Levels of inflammatory cytokines and 'alarmins' were significantly reduced, and the number of F4/80(+) cells was lower under combination therapy (1.8% ± 1.3%; versus 14.6% ± 4.4%; P = 0.0002). This novel inhibitor of the MCP-1/CCR2 axis (mNOX-E36), which has already proven efficacy and tolerability in early clinical trials, alleviates acute rejection processes in allogeneic transplantation especially when combined with subtherapeutic doses of CsA. Thus, mNOX-E36 may have potential as an adjunct immunomodulatory agent.


Subject(s)
Aptamers, Nucleotide/therapeutic use , Chemokine CCL2/antagonists & inhibitors , Graft Survival/drug effects , Immunosuppressive Agents/therapeutic use , Receptors, CCR2/antagonists & inhibitors , Animals , Cyclosporine/therapeutic use , Graft Rejection/immunology , Heart Transplantation , Immunosuppression Therapy/methods , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Transplantation, Homologous
5.
Dtsch Med Wochenschr ; 139(20): 1046-50, 2014 May.
Article in German | MEDLINE | ID: mdl-24801299

ABSTRACT

HISTORY AND CLINICAL FINDINGS: A 50-year-old woman with known tuberous sclerosis complex (TSC) was referred for further work-up of nephrotic syndrome. A left-side nephrectomy due to an anamnestically reported "shrunken kidney" had been performed at the age of 15 years. The patient presented with massive edematous swelling of all extremities and typical cutaneous lesions of TSC. DIAGNOSTIC FINDINGS, TREATMENT AND CLINICAL COURSE: Laboratory analysis revealed nephrotic proteinuria, hypalbuminemia and advanced impairment of kidney function. Computed tomography revealed a massively enlarged remaining kidney with confluent angiomyolipomata. As kidney biopsy was deemed to be too hazardous, a thorough work-up for potentially underlying diseases finally revealed endometrial carcinoma. Hysterectomy resulted in a prompt and sustained decrease of proteinuria and disappearance of edema. CONCLUSION: Although a renal involvement is typical in TSC the occurrence of nephrotic syndrome is not and should give reason for further evaluation.


Subject(s)
Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/surgery , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/surgery , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/surgery , Diagnosis, Differential , Female , Humans , Middle Aged , Treatment Outcome
6.
Transplant Proc ; 45(7): 2795-7, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24034052

ABSTRACT

Headaches are one of the most common medical complaints. The differentiation of benign primary headaches from the small number of patients with secondary headaches may be challenging, but failure to recognize a serious headache can be fatal. We report the case of a 49-year-old renal transplant patient, who was admitted to hospital because of intractable right-sided headaches. Cerebral imaging was unremarkable. Not until 2 days later did the patient develop a rash of grouped vesicles located in the right dermatome C3. Consecutively cerebrospinal fluid tested positive for Varizella zoster virus (VZV), indicating VZV meningitis. Therapy was started with intravenous acyclovir with rapid improvement. Here in we have described an atypical case of VZV reactivation in a renal transplant patient, who initially presented with headaches without any skin manifestation. Because of their compromised immune system, transplant patients have a high risk for visceral involvement of VZV infections, which are a life-threatening emergency. Therefore, vaccination of seronegative patients should be part of the pretransplant workup. Accurate and fast diagnosis of infection is essential to immediately start antiviral therapy.


Subject(s)
Headache/etiology , Kidney Transplantation/adverse effects , Meningitis, Viral/physiopathology , Female , Herpesvirus 3, Human/isolation & purification , Humans , Meningitis, Viral/virology , Middle Aged , Polymerase Chain Reaction
7.
Eur Radiol ; 23(9): 2475-81, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23660773

ABSTRACT

OBJECTIVES: To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. METHODS: Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. RESULTS: Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 ± 21 ml/100 ml/min) compared with those with ATN (77.5 ± 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 ± 3.1 mg/dl in AR and 5.3 ± 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 ± 5.2 mSv; the mean amount of contrast media applied was 34.5 ± 5.1 ml. All examinations were performed without complications. CONCLUSION: CT perfusion of kidney allografts may help to differentiate between ATN and rejection. KEY POINTS: • Quantitative CT perfusion of renal transplants is feasible. • CT perfusion could help to non-invasively differentiate AR from ATN. • CT perfusion might make some renal biopsies unnecessary.


Subject(s)
Graft Rejection/diagnosis , Graft Rejection/physiopathology , Kidney Transplantation/methods , Kidney/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Angiography/methods , Blood Flow Velocity , Contrast Media/pharmacology , Female , Humans , Image Processing, Computer-Assisted , Kidney/blood supply , Kidney Tubular Necrosis, Acute/diagnosis , Kidney Tubular Necrosis, Acute/pathology , Male , Middle Aged , Necrosis , Perfusion , Retrospective Studies , Software , Ultrasonography, Doppler/methods
9.
Transplant Proc ; 44(10): 3048-50, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23195025

ABSTRACT

BACKGROUND: Cutaneous vasculitis is a rare symptom after renal transplantation. With a broad spectrum of differential diagnosis, the new appearance of a skin rash in transplanted patients can be challenging. CASE REPORT: We present the case of a 69-year-old man with palpable purpura, skin ulcerations, and diffuse arthralgias. He had a history of cadaveric renal transplantation owing to biopsy-proven isolated immunoglobulin (Ig)A nephropathy and never suffered from any skin manifestation before. Skin biopsy confirmed Henoch-Schoenlein purpura (HSP), which developed under maintenance immunsuppressive therapy with tacrolimus and mycophenolate mofetil. Renal biopsy showed recurrent IgA nephropathy with positive mesangial and capillary IgA staining. DISCUSSION: This is the first case to describe a new manifestation of HSP following renal transplantation owing to isolated IgA nephropathy. Here, we summarize the differential diagnosis of cutaneous vasculitis following renal transplantation. Moreover we give a short review of the recurrence of IgA nephropathy and HSP after renal transplantation followed by possible strategies for prevention and therapy of recurrent disease.


Subject(s)
Exanthema/immunology , Glomerulonephritis, IGA/surgery , IgA Vasculitis/immunology , Immunoglobulin A/analysis , Kidney Transplantation/immunology , Kidney/immunology , Skin/immunology , Aged , Biomarkers/analysis , Biopsy , Diagnosis, Differential , Drug Therapy, Combination , Exanthema/diagnosis , Exanthema/drug therapy , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/immunology , Humans , IgA Vasculitis/diagnosis , IgA Vasculitis/drug therapy , Immunosuppressive Agents/adverse effects , Kidney/drug effects , Kidney/pathology , Kidney Transplantation/adverse effects , Male , Predictive Value of Tests , Recurrence , Skin/drug effects , Skin/pathology , Treatment Outcome
10.
Dtsch Med Wochenschr ; 135(24): 1224-7, 2010 Jun.
Article in German | MEDLINE | ID: mdl-20533155

ABSTRACT

HISTORY AND CLINICAL FINDINGS: A 70-year-old woman was admitted to hospital with fatigue, pallor and shortness of breath on mild exertion. In her past medical history only borderline hypertension and allergy to penicillin were to note. INVESTIGATIONS: Actual laboratory findings revealed renal failure with metabolic acidosis and hyperkalaemia. A normochrome normocytic anemia and secondary hyperparathyreoidism were suggestive of a subacute course. The renal biopsy showed histological features of a subacute tubulo-interstitial nephritis. DIAGNOSIS, TREATMENT AND COURSE: The chronic renal failure caused by an interstitial nephritis was treated with corticosteroids and hemodialysis treatment was started. The trigger for AIN could not be found, there was no infectious or systemically disease nor a nephrotoxic medication identified. For nearly six months the patient had taken a homeopathic agent which is a dilution of penicillium chrysogenum. In case of a determined allergy to penicillin, an extract of the fungus producing penicillin could possibly cause an interstitial nephritis. The patient was dialysis-independent with a GFR about 8 - 10 ml/min at the time of discharge. CONCLUSION: With interstitial nephritis all agents should be considered a potential suspect, even homeopathic agents.


Subject(s)
Drug Hypersensitivity/complications , Homeopathy , Kidney Failure, Chronic/chemically induced , Nephritis, Interstitial/chemically induced , Penicillins , Penicillium chrysogenum , Phytotherapy/adverse effects , Plant Extracts/toxicity , Aged , Drug Hypersensitivity/diagnosis , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney Failure, Chronic/diagnosis , Nephritis, Interstitial/diagnosis , Risk Factors
11.
Transplant Proc ; 41(6): 2529-32, 2009.
Article in English | MEDLINE | ID: mdl-19715968

ABSTRACT

Recently published data from our center have demonstrated the feasibility of a nephrotoxicity- and atherogenicity-free, mycophenolate mofetil (MMF)-based immunosuppressive protocol for elderly recipients of kidneys from elderly cadaveric donors. We investigated a therapeutic regimen of strictly monitored MMF (target mycophenolic acid [MPA] trough levels between 2-6 microg/mL) and steroids combined with a polyclonal-monoclonal induction regimen consisting of a low-dose, single shot of rabbit ATG (ATG-Fresenius) and the interleukin-2 receptor (IL-2R)-antibody basiliximab (d0 and d4). Between 1997 and 2007, we treated 175 elderly patients with an MMF-based, calcinearin inhibitor (CNI)-free immunosuppressive protocol. For the present cohort, 30 elderly recipients (67.8 +/- 3.8 years) of renal transplants from deceased donors (69.4 +/- 13.3 years) were recruited consecutively for this 5-year prospective, open, single center, pilot trial. One-year results of this clinical trial were patient and renal allograft survivals of 87% and 83%, respectively; death-censored 1-year graft survival was 97%. Mostly steroid-sensitive rejection episodes were observed in 46% of patients, with only 3 patients requiring serum antibody therapy. Renal allograft function was satisfactory, as reflected by a mean serum creatinine of 1.78 +/- 0.45 mg/dL and a Nankivell glomerular filtration rate (GFR) of 48.8 +/- 13.9 mg/dL at 6 months. Twenty-three percent of all patients demonstrated cytomegalovirus (CMV) infections; however, only 3.3% developed CMV disease. Application of a combined polyclonal-monoclonal induction regimen using a nephrotoxicity- and atherogenicity-free, MMF-based immunosuppressive maintenance protocol in elderly cadaveric kidney transplant recipients led to acceptable short-term outcomes, albeit at the expense of an increased rejection rate, comparable to that previously published for elderly (>50 years) recipients of allografts from elderly (>50 years) cadaveric donors.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Mycophenolic Acid/analogs & derivatives , Aged , Aged, 80 and over , Animals , Antibodies, Monoclonal/therapeutic use , Antilymphocyte Serum/therapeutic use , Basiliximab , Cadaver , Calcineurin/immunology , Calcineurin Inhibitors , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Humans , Kidney Function Tests , Kidney Transplantation/mortality , Mycophenolic Acid/therapeutic use , Prospective Studies , Rabbits , Recombinant Fusion Proteins/therapeutic use , Survival Rate , Time Factors , Tissue Donors
13.
Transplant Proc ; 40(10): 3359-61, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19100389

ABSTRACT

Chemokines are involved in the recruitment of inflammatory cells to vascularized allografts. The chemokine CCL2/MCP-1 is expressed during allograft dysfunction, which is associated with the recruitment of inflammatory cells. Both intrinsic renal cells (donor origin) as well as infiltrating inflammatory cells (recipient origin) can be a source of CCL2/MCP-1. We previously demonstrated that the recipient MCP-1-2518G polymorphism is associated with increased CCL2/MCP-1 production by inflammatory cells and decreased renal allograft survival. We evaluated the impact of the MCP-1-2518G polymorphism in donor cells on renal allograft outcomes. We enrolled 252 recipients of kidney allografts in this retrospective study who had received grafts from 152 cadaveric donors. The CCL2/MCP-1 genotype was assessed using genomic DNA isolated from cryopreserved donor splenocytes. Outcome parameters studied were acute biopsy proven rejection (Banff criteria), serum creatinine, and glomerular filtration rate (GFR) at 1 year after transplantation, allograft loss, and death. MCP-1-2518 genotypes were in HW equilibrium. A/A was present in 125 (49.6%), A/G in 107 (42.5%), and G/G in 20 (7.9%) donor kidneys. There were no significant differences in the number of rejection episodes, the number of allograft losses, serum creatinine, GFR, or overall survival 1 year after transplantation. In contrast with the detrimental effect of the CCL2/MCP-1 polymorphism of the recipient, the CCL2/MCP-1 polymorphism of the donor has no impact on the allograft outcome during the first year after transplantation. The impact on the long-term outcomes needs further evaluation.


Subject(s)
Chemokine CCL2/genetics , Kidney Transplantation/physiology , Polymorphism, Single Nucleotide , Chemokines/genetics , DNA Primers , Follow-Up Studies , Glomerular Filtration Rate , Humans , Restriction Mapping , Retrospective Studies , Transplantation, Homologous , Treatment Outcome
14.
Acta Physiol Hung ; 94(1-2): 67-81, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17444276

ABSTRACT

Attraction of mononuclear cells to sites of inflammation requires a close interplay of the inflammatory signal presented via chemokines and specific receptors on effector cells. First studies on acute renal transplant rejection demonstrated the involvement of CC-chemokines, such as RANTES, MIP-1alpha, MIP-1beta and MCP-1, as well as CXC-chemokines such as IL-8 and IP-10, correlating with expression of the corresponding chemokine receptors, CCR1, CCR5 and CCR2 as well as CXCR3. Since then, the pathophysiologic relevance has been extended to chronic allograft nephropathy and transplant glomerulopathy. Chemokine expression can be triggered by different stimuli, e.g. brain death, ischemia, HLA-mismatch and infection. Furthermore, anti-inflammatory chemokines have been identified. Chemokine receptor 7, e.g. enhances homing of lymphocytes to lymphatic tissues and the Duffy antigen receptor, DARC, a non-specific receptor that binds and inactivates different chemokines. While measurement of chemokine expression in clinical transplantation may facilitate the differential diagnosis of allograft dysfunction, knowledge of the chemokine network has also widened the understanding of transplant rejection and opened novel therapeutic approaches. Observations from humans with mutations of the chemokine network as well as transplantation of animals with targeted deletions in this system suggest that manipulations of chemokine signalling may improve the success rates of transplantation. Blocking chemokines unselectively with Met-RANTES or specifically with small molecule inhibitors of various chemokine receptors has lead to improved outcome in animal models. Currently, first human trials are under way to investigate drugs that stimulate lymphocyte homing. Inhibitors of CCR1 and CCR5 are being tested for other human diseases and may eventually be available in transplantation. Nonetheless, chemokine blockade my rather serve as an adjunct in the management of transplant recipients than a new "magic bullet".


Subject(s)
Chemokines/physiology , Kidney Transplantation/physiology , Receptors, Chemokine/physiology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Animals , CCR5 Receptor Antagonists , Chemokines/antagonists & inhibitors , Chemokines/metabolism , Chemotaxis/drug effects , Chemotaxis/physiology , Clinical Trials as Topic , Duffy Blood-Group System , Fingolimod Hydrochloride , Graft Rejection/drug therapy , Graft Rejection/immunology , Graft Rejection/physiopathology , Humans , Models, Animal , Propylene Glycols/therapeutic use , Receptors, CCR1 , Receptors, Cell Surface/deficiency , Receptors, Chemokine/antagonists & inhibitors , Sirolimus/therapeutic use , Sphingosine/analogs & derivatives , Sphingosine/therapeutic use
15.
Transplant Proc ; 39(2): 518-21, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362772

ABSTRACT

BACKGROUND: Chronic allograft nephropathy (CAN) is, among others, caused by nephrotoxic side effects of calcineurin inhibitors (CNI), which are to date still the mainstay of immunosuppressive therapy. Sirolimus (SIR), an immunosuppressive compound without effects on glomerular perfusion, has been used in CNI-sparing immunosuppressive protocols. We report the 5-year follow-up of a prospective, controlled conversion study from CNI to SIR in patients with moderately to severely impaired renal function. METHODS: Twelve renal transplant recipients with moderately to severely impaired renal function (estimated glomerular filtration rate of 17 to 35 mL/min according to the MDRD formula), enrolled in a prospective, controlled 1-year pilot study were followed for 5 years. RESULTS: Three renal grafts (25%) were lost during the 5-year follow-up. Graft loss was due to noncompliance in one patient and to CAN in the other two patients. These two patients returned to dialysis 43 and 59 months after conversion, corresponding to 86 and 75 months after transplantation, respectively. Six of nine patients had a stable or even better renal function compared to the baseline. The lipid profile increased initially, but then remained stable over time. CONCLUSION: Conversion of immunosuppressive therapy from CNI to SIR in patients with impaired renal function more than 1 year after transplantation is feasible and safe yielding improved renal function in the majority of patients, which was sustained at 5 years follow-up.


Subject(s)
Calcineurin Inhibitors , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/physiology , Postoperative Complications/immunology , Sirolimus/therapeutic use , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival/drug effects , Graft Survival/immunology , Humans , Kidney Transplantation/immunology , Time Factors , Transplantation, Homologous
16.
Transplant Proc ; 38(5): 1295-7, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16797286

ABSTRACT

BACKGROUND: Chronic renal transplant dysfunction in part may be due to the nephrotoxic effects of calcineurin inhibitors, which are still the mainstay of immunosuppressive therapy. Sirolimus, a new immunosuppressive compound devoid of significant nephrotoxicity, might therefore exhibit beneficial effects when used in renal transplant recipients with graft dysfunction. METHODS: Twelve renal transplant recipients included in this study had all been receiving calcineurin inhibitors for more than 12 months, and were free of rejection for more than 12 months. However, they demonstrated moderate renal dysfunction with serum creatinine values ranging from 1.8 to 4.0 mg/dL (164 to 351 micromol/L). After reaching a sirolimus level of 10 to 20 ng/mL, calcineurin inhibitor therapy was withheld. RESULTS: One month after initiation of sirolimus therapy, all patients were off calcineurin inhibitors. The average daily sirolimus dosage was 5.8+/-3.4 mg. No acute rejection episode and no graft failure was observed. No patient required hemodialysis or admission to the hospital. Calculated creatinine clearance increased from 63.4+/-9.9 to 69.2+/-9.7 mL/min (P=.0368) and serum bicarbonate increased from 20.8+/-3.17 to 22.5+/-3.7 meq/L (P=.001). Serum cholesterol increased from 180+/-26.5 to 239+/-28.8 mg/dL (4.65+/-0.69 to 6.18+/-0.74 mmol/L, P<.001), triglycerides increased from 155+/-53 to 289+/-123 mg/dL (1.75+/-0.6 to 3.26+/-1.39 mmol/L) and low-density lipoprotein cholesterol increased from 99+/-32 to 131+/-25.1 mg/dL (2.56+/-0.83 to 3.39+/-0.65 mmol/L, P=.01). Arterial blood pressure remained well controlled (126+/-15.6/74+/-8.9 vs 134+/-16.8/83+/-9.7). CONCLUSION: Conversion from calcineurin inhibitor therapy to sirolimus in patients more than 1 year after transplantation with impaired organ function is feasible, safe, and associated with a trend toward improved renal function.


Subject(s)
Kidney Transplantation/physiology , Sirolimus/therapeutic use , Adult , Aged , Azathioprine/adverse effects , Blood Urea Nitrogen , Calcineurin Inhibitors , Creatinine/metabolism , Female , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/immunology , Male , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/analogs & derivatives , Transplantation, Homologous
17.
Clin Infect Dis ; 42(10): 1488-95, 2006 May 15.
Article in English | MEDLINE | ID: mdl-16619164

ABSTRACT

Renal disease is becoming an increasingly prevalent entity in human immunodeficiency virus (HIV)-infected patients; it occurs in a variety of clinical settings and is associated with histopathological changes. HIV-related renal impairment can present as acute or chronic kidney disease; it can be caused directly or indirectly by HIV and/or by drug-related effects that are directly nephrotoxic or lead to changes in renal function by inducing metabolic vaculopathy and renal damage. Acute renal failure is frequently caused by the toxic effects of antiretroviral therapy or nephrotoxic antimicrobial substances used in the treatment of opportunistic infections. Chronic renal disease can be caused by multiple pathophysiological mechanisms, leading to HIV-associated nephropathy, a form of collapsing focal glomerulosclerosis, thrombotic microangiopathy, and various forms of immune complex glomerulonephritis. The increase in life expectancy and alteration of lipid metabolism due to receipt of highly active antiretroviral therapy are expected to result in an increased prevalence of diabetes and hypertension and, thus, to secondary diabetic and hypertensive renal damage. Antiretroviral agents, such as indinavir and tenofovir, have been associated with nephrotoxic drug effects that have been shown to be reversible in most cases. In this article, we review the current knowledge about acute and chronic HIV-associated renal disease, metabolic alterations and related nephropathies, and toxic drug effects of combination antiretroviral pharmacotherapy.


Subject(s)
AIDS-Associated Nephropathy/etiology , Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/drug therapy , AIDS-Associated Nephropathy/epidemiology , Acute Kidney Injury/etiology , Humans , Kidney Failure, Chronic/etiology
18.
Eur J Med Res ; 10(4): 149-54, 2005 Apr 20.
Article in English | MEDLINE | ID: mdl-15946910

ABSTRACT

Gadolinium chelates are widely used in magnetic resonance imaging as contrast medium in patients with nephropathy. However, only few studies have investigated the effect of gadolinium on serum creatinine concentration and estimated GFR as surrogate markers of renal function. This study was performed to evaluate the effect of gadopentetate dimeglumine in a dose sufficient for diagnostic and interventional purposes on renal function in a large sample of patients. We analyzed serum creatinine and serum-urea levels before and after the administration of gadopentetate dimeglumine in patients with normal and patients with pre-existing impaired renal function. Age, height, body mass, sex, medication and preexisting illnesses such as diabetes, renal artery stenosis and heart disease were monitored. In 181 patients with normal renal function, there was no statistically significant change in serum creatinine concentration after the administration of gadopentetate dimeglumine (at baseline: 0.72 +/- 0.18 mg/dl, after gadolinium: 0.73 +/- 0.22 mg/dl). In contrary, serum creatinine levels decreased significantly after the administration of gadolinium in 198 patients with pre-existing renal impairment (1.82 +/- 1.03 mg/dl before and 1.72 +/- 1.03 mg/dl after gadolinium) (p < 0.01). According to this surrogate marker of renal function, the change of estimated GFR in patients with normal baseline renal function was not significant, while in patients with impaired renal function, GFR increased after the administration of gadolinium (p < 0.001). The high diagnostic value of gadolinium contrast media is associated with a very small risk of adverse reactions. Our findings show that the administration of gadolinium even is associated with a decrease of serum creatinine in patients with pre-existing renal impairment. In conclusion, the use of gadolinium-based contrast media may be considered as a safe alternative in patients with impaired renal function for whom use of iodine-based contrast agents is prone to a high rate of radiocontrast-induced nephropathy.


Subject(s)
Contrast Media , Gadolinium DTPA , Kidney Diseases/diagnostic imaging , Kidney Diseases/therapy , Creatinine/blood , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney/metabolism , Kidney Diseases/blood , Magnetic Resonance Imaging , Male , Metabolic Clearance Rate , Middle Aged , Radiography , Retrospective Studies
20.
Transplant Proc ; 36(9): 2659-61, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15621116

ABSTRACT

Percutaneous biopsy of the kidney remains the gold standard to establish a diagnosis in renal diseases. Only semiquantitative assessments of gene expression on biopsies have been possible so far. We studied gene expression of the chemokine fractalkine (FKN) in 12 biopsies from laser microdissected kidney allografts that showed histologic signs of acute rejection and 10 controls. As quantified by real-time PCR, the relative tubular FKN expression increased from 1.0 [0.81 to 2.95] (median [range]) in controls to 12.44 [0.90 to 191.0] in acute rejection (P < .01); glomerular FKN expression from 1.3 [0.07 to 27.44] to 12.22 [1.32 to 50.23] (P < .05); and vascular expression, from 0.72 [0.37 to 5.11] to 7.07 [1.19 to 73.49] (P < .01). Furthermore, there was a trend toward higher glomerular FKN expression among patients with more severe rejection. Our results suggest a role of FKN in acute renal allograft rejection.


Subject(s)
Chemokines, CX3C/genetics , Gene Expression Regulation , Graft Rejection/immunology , Kidney Transplantation/immunology , Laser Therapy/methods , Membrane Proteins/genetics , Acute Disease , Adult , Biopsy , Chemokine CX3CL1 , Creatinine/blood , Female , Graft Rejection/genetics , Graft Rejection/pathology , Humans , Kidney Glomerulus/physiology , Kidney Glomerulus/physiopathology , Kidney Transplantation/pathology , Male , Middle Aged , Proteinuria
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