Clinical effects of sirolimus treatment in patients with increased serum creatinine levels after renal transplant

Abstract Background Belatacept is a new non-nephrotoxic anti-rejection drug that blocks the CD80 / CD86-CD28 complex, that normally activates T lymphocytes. Although the BENEFIT study proposes its use at the forefront of immunosuppressive therapy to prevent renal transplant rejection, the risk of opportunistic infections should not be underestimated, as demonstrated by the following clinical case. Case report We report the case of a 71-year-old male kidney transplant recipient that at 7-month follow-up showed a relevant rise of serum creatinine up to 3.8 mg/dl related to graft rejection. The patient started a cycle of treatment with Belatacept in accomplishment to international studies, with improvement in renal function (serum creatinine: 2.8 mg/dl). After 8 months of therapy, due to the appearance of left brachio-crural hypoasthenia, a brain CT and a brain MRI (both without contrast media because of the severe graft dysfunction) were consecutively performed. Imaging revealed multiple nodular formations in the right hemisphere, compatible with brain abscesses or neuro-lymphoma. Belatacept was promptly suspended, a rachicentesis for liquor analysis performed, and a broad spectrum empiric antibiotic therapy was started on Infectious Disease Specialist advice. After Toxoplasma Gondii positivity was found by PCR on cerebrospinal fluid, neuro-lymphoma was excluded and the patient was switched to a targeted antibiotic therapy with Trimethoprim / Sulfamethoxazole (dose adjusted to renal function) for 6 weeks and subsequently, a maintenance course with Sulfadiazine and Pyrimethamine. During treatment, brain lesions showed progressive reduction, with marked clinical improvement and stabilization of renal function (eGFR 25 ml / min). Conclusions As far as is known in the literature, this is the first case of Toxoplasma Gondii brain infection that can be correlated with the use of Belactacept. The appearance of a severe opportunistic infection, in a short period of time after the introduction of Belatacept, could indicate the direct role of Belatacept in the development of these brain abscesses and indicates the importance of carefully evaluating the use of the drug in elderly patients with reduced renal function, in which adequate prophylactic therapy would be particularly indicated.

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Prediction of mizoribine pharmacokinetic parameters by serum creatinine in renal transplant recipients

European Journal of Clinical Pharmacology ◽

10.1007/s00228-018-2584-4 ◽

2018 ◽

Vol 75 (3) ◽

pp. 363-369 ◽

Cited By ~ 2

Author(s):

Pan Chen ◽

Xuan Xu ◽

Longshan Liu ◽

Jingjing Wu ◽

Jingjie Li ◽

...

Keyword(s):

Renal Transplant ◽

Serum Creatinine ◽

Pharmacokinetic Parameters ◽

Renal Transplant Recipients ◽

Transplant Recipients

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Biopsy Induced Arteriovenous Fistula and Venous Stenosis in a Renal Transplant

Case Reports in Nephrology ◽

10.1155/2015/313610 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3

Author(s):

Sridhar R. Allam ◽

Balamurugan Sankarapandian ◽

Imran A. Memon ◽

Patrick C. Nef ◽

Tom S. Livingston ◽

...

Keyword(s):

Renal Transplant ◽

Serum Creatinine ◽

Arteriovenous Fistula ◽

Renal Vein ◽

Deceased Donor ◽

Coil Occlusion ◽

Stage Renal Disease ◽

End Stage ◽

Vein Stenosis ◽

Transplant Biopsy

Renal transplant vein stenosis is a rare cause of allograft dysfunction. Percutaneous stenting appears to be safe and effective treatment for this condition. A 56-year-old Caucasian female with end stage renal disease received a deceased donor renal transplant. After transplant, her serum creatinine improved to a nadir of 1.2 mg/dL. During the third posttransplant month, her serum creatinine increased to 2.2 mg/dL. Renal transplant biopsy showed BK nephropathy. Mycophenolate was discontinued. Over the next 2 months, her serum creatinine crept up to 6.2 mg/dL. BK viremia improved from 36464 copies/mL to 15398 copies/mL. A renal transplant ultrasound showed lower pole arteriovenous fistula and abnormal waveforms in the renal vein. Carbon dioxide (CO2) angiography demonstrated severe stenosis of the transplant renal vein. Successful coil occlusion of fistula was performed along with angioplasty and deployment of stent in the renal transplant vein. Serum creatinine improved to 1.5 mg/dL after.

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Homocysteine in the Plasma of Renal Transplant Recipients: Effects of Cofactors for Methionine Metabolism

Clinical Science ◽

10.1042/cs0610743 ◽

1981 ◽

Vol 61 (6) ◽

pp. 743-749 ◽

Cited By ~ 97

Author(s):

D. E. L. Wilcken ◽

Vatsala J. Gupta ◽

A. K. Betts

Keyword(s):

Folic Acid ◽

Amino Acid ◽

Renal Transplant ◽

Serum Creatinine ◽

Vitamin B12 ◽

Normal Subjects ◽

Serum Folate ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Erythrocyte Folate

1. Homocysteine which is formed during the metabolism of methionine is readily oxidized and is measured by the amino acid analyser as cysteine—homocysteine mixed disulphide and homocystine. We measured plasma amino acid concentrations after an overnight fast in 27 stable long-term renal transplant recipients and 25 age-and sex-matched normal subjects with particular emphasis on sulphur-containing amino acids. 2. Plasma cysteine—homocysteine mixed disulphide was increased in the patients (mean 6.0 ± sd 3.2 μmol/l; normal 3.1 ± 0.9 μmol/l, P < 0.001) and homocystine was detectable in low concentration (< 1.0 μmol/l) in 24; the elevation in cysteine—homocysteine was related to serum creatinine (r = 0.60, P < 0.002). Cystine was also increased (91.6 ± 29.3 μmol/l; normal subjects 64.0 ± 16.7 μmol/l, P < 0.001), but methionine concentrations were normal. 3. When pyridoxine, folic acid and vitamin B12, cofactors for homocysteine metabolism, were administered sequentially to 11 arbitrarily selected transplant recipients cysteine—homocysteine decreased from 7.3 ± 2.1 to 4.3 ± 0.8 μmol/l (P < 0.001) and homocystine became undetectable. the response coincided with the giving of folic acid and occurred without alteration in serum creatinine and with normal serum folate and vitamin B12 concentrations. 4. in eight patients in whom pretreatment erythrocyte folate was measured, folic acid therapy reduced cysteine—homocysteine from 9.0 ± 3.1 to 5.4 ± 1.6 μmol/l over a 4 week period (P < 0.001), the largest response being in the one patient with subnormal erythrocyte folate; values were in the low-normal or normal range in the other seven. 5. We conclude that plasma homocysteine is increased in renal transplant recipients when serum creatinine is only moderately elevated and that the homocysteine concentrations are decreased by treatment with folic acid, suggesting that both reduced homocysteine excretion and relative shortages of folic acid are responsible.

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Serum Cystatin C as a Determinant of Fasting Total Homocysteine Levels in Renal Transplant Recipients with a Normal Serum Creatinine

Journal of the American Society of Nephrology ◽

10.1681/asn.v101164 ◽

1999 ◽

Vol 10 (1) ◽

pp. 164-166 ◽

Cited By ~ 1

Author(s):

ANDREW G. BOSTOM ◽

REGINALD Y. GOHH ◽

LINDA BAUSSERMAN ◽

DAVID HAKAS ◽

PAUL F. JACQUES ◽

...

Keyword(s):

Renal Transplant ◽

Serum Creatinine ◽

Cystatin C ◽

Normal Serum ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Total Homocysteine ◽

Plasma Total Homocysteine

Abstract. Serum creatinine, a surrogate for both renal function and homocysteine generation, is an important determinant of fasting plasma total homocysteine levels in stable renal transplant recipients. In this study, it is hypothesized that among stable renal transplant recipients with normal creatinine levels (i.e., ≤ 1.5 mg/dl), serum cystatin C, a more sensitive indicator of GFR, would better predict fasting total homocysteine levels compared with serum creatinine. Fasting plasma total homocysteine, folate, vitamin B12, and pyridoxal 5′-phosphate levels, along with serum cystatin C, creatinine, and albumin levels, were determined in 28 consecutive renal transplant recipients (mean age 47 ± 14 yr; 60.7% men) with stable allograft function, whose serum creatinine was ≤1.5 mg/dl. General linear modeling with analysis of covariance revealed that serum cystatin C was independently predictive (partial R = 0.494; P = 0.023) of fasting total homocysteine levels after adjustment for age, gender, vitamin status, albumin, and creatinine levels. In contrast, creatinine levels were not predictive of fasting total homocysteine levels in this model (P = 0.110) or an identical model that excluded cystatin C (P = 0.131). Serum cystatin C levels may reflect subtle decreases in renal function that independently predict fasting total homocysteine levels among stable renal transplant recipients with a normal serum creatinine.

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Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program

Saudi Journal of Kidney Diseases and Transplantation ◽

10.4103/1319-2442.301204 ◽

2020 ◽

Vol 31 (5) ◽

pp. 998

Author(s):

SyedHaider Nawaz ◽

MirzaNaqi Zafar ◽

Mohammad Afzal ◽

SyedAli Anwar Naqvi ◽

Muhammed Mubarak ◽

...

Keyword(s):

Renal Transplant ◽

Serum Creatinine ◽

Graft Survival ◽

Renal Graft ◽

Transplant Program ◽

One Year ◽

Living Related ◽

Renal Graft Survival

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P0193MEASUREMENTS OF SERUM CREATININE AND EGFR IN PATIENTS WITH CHRONIC CARDIORENAL SYNDROME TYPE 2 ARE INSUFFICIENT TO ASSESS RENAL RESPONSES TO RESYNCHRONIZATION THERAPY DURING A TREE-MONTH FOLLOW-UP

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0193 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Agnieszka Gala-Błądzińska ◽

Tomasz Kubrak ◽

Joanna Czech ◽

Krzysztof Gargasz ◽

Danuta Mazur ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Cardiac Resynchronization Therapy ◽

Cystatin C ◽

Cardiac Resynchronization ◽

Prostaglandin D2 ◽

Clinical Effects ◽

Resynchronization Therapy

Abstract Background and Aims Chronic cardiorenal sydrome type 2 (CRS-T2) has a complex pathophysiology. Treatment and evaluation of the clinical effects of CRS-T2 therapy is difficult in clinical practice. The study’s aim was to non-invasively assess renal function using biomarkers associated with nephron injury sites in patients with CRS-T2 following cardiac resynchronization therapy (CRT). Method The study included patients with CRS-T2 and heart failure in NYHA classes II-IV, in whom CRT devices had been implanted. Before cardiac resynchronization therapy and after 3 months, patients’ renal function was assessed using biomarkers measured in single urine and blood samples. Test results were correlated with cardiovascular fitness assessments. Results CRT was implanted in 56 (n = 17; 30.4% ♀) patients with a mean age of 66 ± 10 years with CRS-T2 in the course of coronary artery disease (n = 38) or dilated cardiomyopathy (n = 18) with eGFRCKD-EPI = 68.55 ± 20.34 ml / min / 1.73m2. The three-month follow-up was continued in 33 (61.11%) patients. Three months after implantation CRT, the responders group cardiovascular endurance improved by at least on NYHA class; showed a significant decrease in NT-pro BNP (n = 24; 72.72%; p = 0.004), a significant (p < 0.05) decrease in serum prostaglandin D2 synthase (sPGD2S) and albuminuria (uACR) concentrations (Figure 1 a), and increases in hematocrit (HCT), erythrocyte count (RBC) and hemoglobin (Hb). The urine samples of the non-responders group following CRT, showed significant (p <0.05) increases in lipocalin concentrations associated with neutrophil gelatinase (uNGAL), and a decrease in cystatin C (uCysC) concentrations (Figure 1 b). There were no significant changes in the concentration of serum creatinine (sCr), eGFRCKD-EPI, serum cystatin C or uromodulin in urine and serum; and urinary kidney injury molecule-1 (uKIM-1) was found in the urine of both responding and nonresponding groups (p> 0.05). Conclusion The sCR and eGFR CKD-EPI assessment should not be used to assess renal function in patients with type 2 chronic cardiac renal syndrome who have undergone CRT implantation. Renal function biomarkers that account for the pathophysiology of nephron injury and correlated with myocardial function: sPGD2S, uACR, uCysC, uNGAL. Also, increased HCT, RBC, and Hb are characteristic in responders.

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Renal transplant biopsy complications: assessment of risk factors and potential of desmopressin to decrease risk of hemorrhage

Acta Radiologica ◽

10.1177/0284185120910590 ◽

2020 ◽

Vol 61 (12) ◽

pp. 1717-1723

Author(s):

Björn Peters ◽

Salmir Nasic ◽

Gert Jensen ◽

Bernd Stegmayr

Keyword(s):

Risk Factor ◽

Renal Transplant ◽

Serum Creatinine ◽

Resistive Index ◽

Major Complication ◽

Binary Logistic Regression ◽

P Value ◽

Arterial Blood ◽

Risk Of Hemorrhage ◽

Biopsy Complications

Background Renal transplant biopsies are essential in nephrology; however, they are invasive and complications can occur. Purpose To explore the risk of transplant kidney biopsy (TxB) complications in relation to possible preventive effects of desmopressin prophylaxis. Material and Methods A total of 515 consecutive TxB (375 patients, median age 53 years) were analyzed. In 252 TxB, the Resistive Index (RI) was measured right before the biopsy. A total of 282 patients had serum creatinine >150 µmol/L. In one of the six hospitals 39/282 patients consecutively received desmopressin (dose 0.3 µg/kg subcutaneously) as prophylaxis within 1 h before the biopsy. Fisher’s exact and χ2 test were used (odds ratio [OR], 95% confidence interval [CI]). Univariate and multiple binary logistic regression analyses were performed. A two-sided P value <0.05 was considered significant. Results RI ≥ 0.8 was a risk factor for major TxB complications (OR 4.2, 95% CI 1.13–15.76). The risk for minor complications decreased with mean arterial blood pressure (MAP) (97.9 vs. 89.5 mmHg, OR 0.97, 95% CI 0.95–0.997). In a multiple regression analysis for overall biopsy complications, the risk remained increased for patients with RI ≥ 0.8 (OR 4.45, 95% CI 1.32–15.04). No patients (0/39) with desmopressin prophylaxis had a major complication versus 8/243 in the other group. In patients with serum creatinine >150 µmol/L, those with a higher MAP had more overall TxB complications (104.5 vs. 98.2 mmHg, OR 1.05, 95% CI 1.004–1.1). Conclusion RI ≥ 0.8 was a risk factor for major and overall complications and a lower MAP for minor biopsy complications. Desmopressin prophylaxis showed yet no verified benefit as prophylaxis in TxB.

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CAN SERUM CREATININE IN THE FIRST YEAR AFTER TRANSPLANT PREDICT LONG-TERM RENAL TRANSPLANT OUTCOME?

Transplantation Journal ◽

10.1097/00007890-200407271-00844 ◽

2004 ◽

Vol 78 ◽

pp. 317

Author(s):

R J. Johnson ◽

C J. Rudge ◽

D Collett ◽

J L.R. Forsythe

Keyword(s):

Renal Transplant ◽

Serum Creatinine ◽

First Year ◽

Transplant Outcome

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