A joint transition model for evaluating eGFR as biomarker for rejection after kidney transplantation

The estimated glomerular filtration rate (eGFR) quantifies kidney graft function and is measured repeatedly after transplantation. Kidney graft rejection is diagnosed by performing biopsies on a regular basis (protocol biopsies at time of stable eGFR) or by performing biopsies due to clinical cause (indication biopsies at time of declining eGFR). The diagnostic value of the eGFR evolution as biomarker for rejection is not well established. To this end, we built a joint model which combines characteristics of transition models and shared parameter models to carry over information from one biopsy to the next, taking into account the longitudinal information of eGFR collected in between. From our model, applied to data of University Hospitals Leuven (870 transplantations, 2 635 biopsies), we conclude that a negative deviation from the mean eGFR slope increases the probability of rejection in indication biopsies, but that, on top of the biopsy history, there is little benefit in using the eGFR profile for diagnosing rejection. Methodologically, our model fills a gap in the biomarker literature by relating a frequently (repeatedly) measured continuous outcome with a less frequently (repeatedly) measured binary indicator. The developed joint transition model is flexible and applicable to multiple other research settings.

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MO937ASSOCIATION OF RENAL ELASTOGRAPHY WITH BANFF MICROVASCULAR INFLAMMATION IN PROTOCOL BIOPSIES FOR SUBCLINICAL RENAL GRAFT REJECTION DIAGNOSIS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0016 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Lucino Bahena Carrera ◽

Javier Bastida Alquicira

Keyword(s):

Graft Rejection ◽

Kidney Graft ◽

Non Invasive ◽

Renal Graft ◽

Protocol Biopsies ◽

Subclinical Rejection ◽

The Mean ◽

Microvascular Inflammation ◽

Renal Graft Rejection ◽

Acute Graft

Abstract Background and Aims The most common cause of renal graft failure is chronic dysfunction in 24.7% and the most common etiology of this is clinical or subclinical rejection. The incidence of subclinical rejection varies from 15 to 50% (25% in protocol biopsies in the first year after transplantation and 35% after two years). Melek E et al have shown that doppler ultrasound is a non-invasive study that, through the resistance index (RI), has traditionally been used for the early diagnosis of acute graft rejection (AR); however, it is influenced by extrarenal systemic factors. Naesens et al published that in 321 kidney transplant recipients, RI wasn´t associated with histological findings of AR in protocol biopsies. Elastography is another ultrasonographic modality for the evaluation of the kidney graft, which measures the stiffness/elasticity of the tissue expressed in Kpa (kilopascals). Stock in 2011 and Kim BJ in 2018 published studies where they showed that increased stiffness was correlated with the diagnosis of kidney graft rejection. The aim of this study was to describe the association between elastography with microvascular inflammation determined by Banff for diagnosis of renal allograft subclinical rejection. Method Observational, analytical and cross-sectional study that included kidney transplant patients who underwent protocol biopsy and renal elastography at the Central Military Hospital in Mexico City between January 2018 and December 2020. The demographic and biochemical characteristics, degree elastography stiffness and Banff 2017 lesions were determined. The sample calculation, determination of correlation degree and ROC curve elaboration were performed. Results We included 146 patients. 56.8% were men; the most common causes of CKD were undetermined and chronic glomerulonephritis with 52.7% and 17.1% respectively. 47.3% were hypertensive at biopsy time and 1.4% had chronic heart failure. The most common immunosuppression schemes were FK/MPA/steroid and FK/mTOR-i/steroid with 60.3% and 13%, respectively. The mean GFR was 65.31 ml/min which shows graft good function. The mean stiffness in the elastography was 15.73 Kpa. The rest of baseline data are shown in Table 1. Had rejection 36.3% of the biopsies, the most frequent chronic AMR C4d- with 15.1% and active AMR C4d- 8.9%. When analyzing the ROC curves, the Banff 2017 lesions AUC values that correlated better with graft stiffness were: v=0.607, i=0.594, g=0.578, C4d deposit=0.519, ptc=0.498. Figure 1. Conclusion Intimal arteritis, inflammation, and glomerulitis are the Banff lesions best associated with elastography graft stiffness in protocol biopsies. Prospective studies are recommended in patients with acute graft dysfunction to find an adequate elastography cut-off value that allows another tool for fast and non-invasive diagnosis of renal graft rejection.

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The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series

Journal of Clinical Medicine ◽

10.3390/jcm9020529 ◽

2020 ◽

Vol 9 (2) ◽

pp. 529 ◽

Cited By ~ 2

Author(s):

Aureliusz Kolonko ◽

Natalia Słabiak-Błaż ◽

Henryk Karkoszka ◽

Andrzej Więcek ◽

Grzegorz Piecha

Keyword(s):

Estimated Glomerular Filtration Rate ◽

Case Series ◽

Primary Treatment ◽

Kidney Graft ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection ◽

The Mean ◽

Mid Term Results

Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial.

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Estimated Renal Metabolomics at Reperfusion Predicts One-Year Kidney Graft Function

Metabolites ◽

10.3390/metabo12010057 ◽

2022 ◽

Vol 12 (1) ◽

pp. 57

Author(s):

Thomas Verissimo ◽

Anna Faivre ◽

Sebastian Sgardello ◽

Maarten Naesens ◽

Sophie de Seigneux ◽

...

Keyword(s):

Renal Function ◽

Learning Algorithm ◽

Standard Procedure ◽

Graft Function ◽

Training Dataset ◽

Kidney Graft ◽

Kidney Recipients ◽

Protocol Biopsies ◽

Patients At Risk ◽

One Year

Renal transplantation is the gold-standard procedure for end-stage renal disease patients, improving quality of life and life expectancy. Despite continuous advancement in the management of post-transplant complications, progress is still needed to increase the graft lifespan. Early identification of patients at risk of rapid graft failure is critical to optimize their management and slow the progression of the disease. In 42 kidney grafts undergoing protocol biopsies at reperfusion, we estimated the renal metabolome from RNAseq data. The estimated metabolites’ abundance was further used to predict the renal function within the first year of transplantation through a random forest machine learning algorithm. Using repeated K-fold cross-validation we first built and then tuned our model on a training dataset. The optimal model accurately predicted the one-year eGFR, with an out-of-bag root mean square root error (RMSE) that was 11.8 ± 7.2 mL/min/1.73 m2. The performance was similar in the test dataset, with a RMSE of 12.2 ± 3.2 mL/min/1.73 m2. This model outperformed classic statistical models. Reperfusion renal metabolome may be used to predict renal function one year after allograft kidney recipients.

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Effect of Calcium-Channel Blockers on Cyclosporine Clearance and Use in Renal Transplant Patients

Annals of Pharmacotherapy ◽

10.1177/106002809402801101 ◽

1994 ◽

Vol 28 (11) ◽

pp. 1227-1231 ◽

Cited By ~ 28

Author(s):

Ingrida S. Sketris ◽

Michelle E. Methot ◽

David Nicol ◽

Philip Belitsky ◽

Margot G. Knox

Keyword(s):

Calcium Channel ◽

Continuous Infusion ◽

Calcium Channel Blockers ◽

Graft Function ◽

Control Group ◽

Channel Blockers ◽

Kidney Graft ◽

Blood Concentrations ◽

Significant Difference ◽

The Mean

OBJECTIVE: To determine the effect of calcium-channel blockers (CCBs) on cyclosporine dose, clearance, and cost, and their effect on kidney graft function and survival in patients who underwent kidney transplant. DESIGN: A total of 176 adults receiving 177 transplants were studied retrospectively. Patients were stratified as follows: no CCB (n=57), diltiazem (n=13), nifedipine (n=37), and verapamil (n=70). Patients received cyclosporine 3–4 mg/kg by continuous infusion for 5 days followed by cyclosporine 10 mg/kg/d po to maintain initial whole blood concentrations of 300–400 ng/mL. Clearance of intravenously administered cyclosporine was calculated following at least 48 hours of the same dose by continuous infusion. The amount and cost of cyclosporine used during the first 10 days of oral therapy were also calculated. RESULTS: Patients receiving diltiazem, but not verapamil or nifedipine, had decreased clearance of intravenously administered cyclosporine compared with that of the mean control group. The mean clearance of intravenously administered cyclosporine ± SD in patients receiving no CCB was 5.1 ± 1.5 mL/min/kg, diltiazem was 3.7 ± 0.8 mL/min/kg, nifedipine was 6.4 ± 1.9 mL/min/kg, and verapamil was 5.2 ± 2.2 mL/min/kg. The amount and cost of 10 days of oral cyclosporine therapy was decreased in the verapamil group (5.7 ± 1.5 g and $257 ± 69) compared with that of the control group (6.7 ± 1.6 g and $304 ± 72) (p<0.001). There was no significant difference among the groups with respect to immediate graft function, 1-year serum creatinine concentration, or 1-year graft survival. CONCLUSIONS: Diltiazem decreased the clearance of intravenously administered cyclosporine. Although verapamil did not decrease the clearance of intravenously administered cyclosporine, it allowed a significant reduction in oral cyclosporine cost without apparent adverse effects on graft function. Further work is needed to determine the effect of CCBs on cyclosporine pharmacokinetics, especially with respect to their metabolism by gut and hepatic cytochrome P-450 enzymes, and their effect on patient outcome.

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Publication activity of chief and consultant general/visceral surgeons in German university hospitals—a ten-year analysis

Langenbeck s Archives of Surgery ◽

10.1007/s00423-021-02241-6 ◽

2021 ◽

Author(s):

Eva C. Böckmann ◽

E. S. Debus ◽

R. T. Grundmann

Keyword(s):

Impact Factor ◽

Publication Activity ◽

University Hospitals ◽

Cumulative Impact ◽

University Departments ◽

The Third ◽

Publication Number ◽

Significant Difference ◽

The Mean ◽

Number Of Publications

Abstract Purpose The publication activity of 38 German general/visceral surgery university departments, documented by first or last authorship from staff surgeons (chief and consultants), was evaluated. Methods The observation period extended from 2007 to 2017 and all PubMed-listed publications were considered. Impact factor (IF) was evaluated through the publishing journal’s 5-year IF in 2016, as was the IF for each individual publication. Ranking was expressed in quartiles. Results The staff surgeons of the 38 departments comprised 442 surgeons, of which only 351 (79.4%) were active as first or last authors. Four thousand six hundred and ninety-nine publications published in 702 journals were recorded. The four leading departments in publication number published as much as the last 20 departments (1330 vs. 1336 publications, respectively). The mean of the first (most active) department quartile was 19.6 publications, the second 15.4, the third 11.0, and the last quartile 7.6 per publishing surgeon. The total cumulative impact factor was 14,130. When examining the mean number of publications per publishing surgeons per the 10 year period, the mean of the first quartile was 57.9 cumulative IF, the second 45.0, the third 29.5, and the fourth quartile 17.1. With 352 (7.5%) publications, the most frequently used journal was Chirurg, followed by Langenbeck’s Archives of Surgery with 274 (5.8%) publications. Pancreas-related topics led in terms of publication number and IF generated per individual publication. Conclusion A significant difference in publication performance of individual departments was apparent that cannot be explained by staff number. This indicates that there are as yet unknown factors responsible for minor publication activity in many university departments.

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Outcomes in Living Donor Kidney Transplantation: The Role of Donor’s Kidney Function

Kidney & Blood Pressure Research ◽

10.1159/000512177 ◽

2021 ◽

pp. 1-11

Author(s):

Massimo Torreggiani ◽

Ciro Esposito ◽

Elena Martinelli ◽

Thomas Jouve ◽

Antoine Chatrenet ◽

...

Keyword(s):

Kidney Transplant ◽

Kidney Function ◽

Living Donor ◽

Graft Function ◽

Kidney Graft ◽

Donor Kidney ◽

Transplant Center ◽

Function Correlation ◽

End Stage ◽

Living Donor Kidney

Introduction: Living donor kidney transplant (LDKT) is one of the best therapeutic options for end-stage kidney disease (ESKD). Guidelines identify different estimated glomerular filtration rate (eGFR) thresholds to determine the eligibility of donors. The aim of our study was to evaluate whether pretransplant donor eGFR was associated with kidney function in the recipient. Methods: We retrospectively studied LDKT recipients who received a kidney graft between September 1, 2005, and June 30, 2016 in the same transplant center in France and that had eGFR data available at 3, 12, 24, and 36 months posttransplant. Results: We studied 90 donor-recipient pairs. The average age at time of transplant was 51.47 ± 10.95 for donors and 43.04 ± 13.52 years for recipients. Donors’ average eGFR was 91.99 ± 15.37 mL/min/1.73 m2. Donor’s age and eGFR were significantly correlated (p < 0.0001, r2 0.023). Donor’s age and eGFR significantly correlated with recipient’s eGFR at 3, 12, and 24 months posttransplant (age: p < 0.001 at all intervals; eGFR p = 0.001, 0.003, and 0.016, respectively); at 36 months, only donor’s age significantly correlated with recipient’s eGFR. BMI, gender match, and year of kidney transplant did not correlate with graft function. In the multivariable analyses, donor’s eGFR and donor’s age were found to be associated with graft function; correlation with eGFR was lost at 36 months; and donor’s age retained a strong correlation with graft function at all intervals (p < 0.001). Conclusions: Donor’s eGFR and age are strong predictors of recipient’s kidney function at 3 years. We suggest that donor’s eGFR should be clinically balanced with other determinants of kidney function and in particular with age.

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Associations among Heavy Metals and Proteinuria and Chronic Kidney Disease

Diagnostics ◽

10.3390/diagnostics11020282 ◽

2021 ◽

Vol 11 (2) ◽

pp. 282

Author(s):

Hui-Ju Tsai ◽

Chih-Hsing Hung ◽

Chih-Wen Wang ◽

Hung-Pin Tu ◽

Chiu-Hui Li ◽

...

Keyword(s):

Heavy Metals ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

General Population ◽

Estimated Glomerular Filtration Rate ◽

Synergistic Effects ◽

Blood Lead ◽

Southern Taiwan ◽

The Mean ◽

Traditional Risk Factors

Background: The prevalence of chronic kidney disease (CKD) is increasing annually in Taiwan. In addition to traditional risk factors, heavy metals contribute to the development of CKD. The aim of this study was to investigate associations among heavy metals and proteinuria and CKD in the general population in Southern Taiwan. We also explored the interaction and synergetic effects among heavy metals on proteinuria. Methods: We conducted a health survey in the general population living in Southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb) and urine nickel (Ni), chromium (Cr), manganese (Mn), arsenic (As), copper (Cu), and cadmium (Cd). Proteinuria was measured using reagent strips. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Results: The mean age of the 2447 participants was 55.1 ± 13.2 years and included 977 males and 1470 females. Participants with high blood Pb and high urine Ni, Mn, Cu, and Cd were significantly associated with proteinuria. Interactions between blood Pb and urine Cr, and between urine Cd and Cu, had significant effects on proteinuria. The participants with high blood Pb and high urine Cu were significantly associated with an eGFR of <60 mL/min/1.73 m2. Conclusion: High blood Pb and high urine Cu may be associated with proteinuria and an eGFR of <60 mL/min/1.73 m2. High urine Ni, Mn, and Cd were significantly associated with proteinuria. Co-exposure to Cd and Cu, and Pb and Cr, may have synergistic effects on proteinuria.

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Activation of final complement components after kidney transplantation as a marker of delayed graft function severity

Clinical Kidney Journal ◽

10.1093/ckj/sfaa147 ◽

2020 ◽

Author(s):

Carlos E Arias-Cabrales ◽

Marta Riera ◽

María José Pérez-Sáez ◽

Javier Gimeno ◽

David Benito ◽

...

Keyword(s):

Epithelial Cells ◽

Graft Function ◽

Basal Membrane ◽

Factor H ◽

Delayed Graft Function ◽

Control Group ◽

Complement Factor ◽

Tubular Epithelial Cells ◽

Complement Components ◽

Protocol Biopsies

Abstract Background Ischaemia–reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients. Methods We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies (n = 12) and a control group of 1-year protocol biopsies without tissue damage (n = 4) were stained for C5b-9, C3b and FH. Results SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142 mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0–7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients. Conclusions Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.

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Conversion from calcineurin inhibitors to sirolimus of recipients with chronic kidney graft disease grade iii for a period 2003-2011

Vojnosanitetski pregled ◽

10.2298/vsp1309848i ◽

2013 ◽

Vol 70 (9) ◽

pp. 848-853 ◽

Cited By ~ 1

Author(s):

Ljiljana Ignjatovic ◽

Rajko Hrvacevic ◽

Dragan Jovanovic ◽

Zoran Kovacevic ◽

Neven Vavic ◽

...

Keyword(s):

Serum Creatinine ◽

Immunosuppressive Therapy ◽

Graft Function ◽

Solid Organ Transplantation ◽

Calcineurin Inhibitors ◽

Solid Organ ◽

Kidney Graft ◽

Group I ◽

Grade Iii

Background/Aim. Tremendous breakthrough in solid organ transplantation was made with the introduction of calcineurin inhibitors (CNI). At the same time, they are potentially nephrotoxic drugs with influence on onset and progression of renal graft failure. The aim of this study was to evaluate the outcome of a conversion from CNIbased immunosuppressive protocol to sirolimus (SRL) in recipients with graft in chronic kidney disease (CKD) grade III and proteinuria below 500 mg/day. Methods. In the period 2003-2011 24 patients (6 famale and 18 male), mean age 41 ? 12.2 years, on triple immunosuppressive therapy: steroids, antiproliferative drug [mycophenolate mofetil (MMF) or azathiopirine (AZA)] and CNI were switched from CNI to SRL and followe-up for 76 ? 13 months. Nine patients (the group I) had early postransplant conversion after 4 ? 3 months and 15 patients (the group II) late conversion after 46 ? 29 months. During the regular outpatient controls we followed graft function through the serum creatinine and glomerular filtration rate (GFR), proteinuria, lipidemia and side effects. Results. Thirty days after conversion, in all the patients GFR, proteinuria and lipidemia were insignificantly increased. In the first two post-conversion months all the patients had at least one urinary or respiratory infection, and 10 patients reactivated cytomegalovirus (CMV) infection or disease, and they were successfully treated with standard therapy. After 21 ? 11 months 15 patients from both groups discontinued SRL therapy due to reconversion to CNI (10 patients) and double immunosuppressive therapy (3 patients), return to hemodialysis (1 patient) and death (1 patient). Nine patients were still on SRL therapy. By the end of the follow-up they significantly improved GFR (from 53.2 ? 12.7 to 69 ? 15 mL/min), while the increase in proteinuria (from 265 ? 239 to 530.6 ? 416.7 mg/day) and lipidemia (cholesterol from 4.71 ? 0.98 to 5.61 ? 1.6 mmol/L and triglycerides from 2.04 ? 1.18 to 2.1 ? 0.72 mmol/L) were not significant. They were stable during the whole follow-up period. Ten patients were reconverted from SRL to CNI due to the abrupt increase of proteinuria (from 298 ? 232 to 1639 ? 1641/mg day in 7 patients), rapid growth of multiple ovarian cysts (2 patients) and operative treatment of persisted hematoma (1 patient). Thirty days after reconversion they were stable with an insignificant decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/min) and significantly improved proteinuria (from 1639 ? 1641 to 529 ? 688 mg/day). By the end of the follow-up these patients showed nonsignificant increase in the serum creatinine (from 172 ? 88 to 202 ? 91 mmol/L), decrease in GFR (from 56.10 ? 28.09 to 47 ? 21 mL/day) and increased proteinuria (from 528.9 ? 688 to 850 ? 1083 mg/min). Conclusion. In this small descriptive study, conversion from CNI to SRL was followed by an increased incidence of infections and consecutive 25-50% dose reduction in the second antiproliferative agent (AZA, MMF), with a possible influence on the development of glomerulopathy in some patients, which was the major reason for discontinuation of SRL therapy in the 7 (29%) patients. Nine (37.5%) of the patients experienced the greatest benefit of CIN to SRL conversion without serious post-conversion complications.

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STUDIES IN THE RELATION OF THE HEMOLYTIC STREPTOCOCCUS TO RHEUMATIC FEVER

PEDIATRICS ◽

10.1542/peds.3.4.482 ◽

1949 ◽

Vol 3 (4) ◽

pp. 482-503

Author(s):

T. N. HARRIS ◽

SUSANNA HARRIS ◽

RUTH L. NAGLE

Keyword(s):

Rheumatic Fever ◽

Streptococcal Infection ◽

Laboratory Diagnosis ◽

Diagnostic Value ◽

The Other ◽

Streptococcal Infections ◽

Hemolytic Streptococcus ◽

Streptococcal Antigens ◽

The Mean

Titrations of antibodies to four streptococcal antigens have been carried out in the sera of patients with rheumatic fever and of convalescents from streptococcal infections. These antigens are the hyaluronidase, the hemolysin, and two somatic fractions, the cytoplasmic particles and supernate proteins. Mean titers to all of these antigens were elevated in both rheumatic and streptococcal infection. The mean titer was somewhat higher in rheumatic than in streptococcal infection in the case of three of these antibodies. In the case of the fourth, antihyaluronidase, this difference was considerably greater. The antihyaluronidase titer showed better correlation with changes in the activity of the rheumatic infection than did the other tests. There was, however, no striking correlation between this titer and the severity of the illness. Application was made of these findings to the problem of laboratory diagnosis of rheumatic fever by streptococcal serology. A method is presented for assessing the relative usefulness of such tests in terms of the, distribution of their titers in this disease and in health. By this method the antihyaluronidase test was found to be most useful of the four. The comparative diagnostic value for rheumatic fever was studied in the case of the antihyaluronidase test, the antistreptolysin test, and of combinations of both tests.

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