Evaluation of Safety and Beneficial Health Effects of the Human-Milk Strain Bifidobacterium breve DSM32583: An Infant Pilot Trial.

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 107 cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG (p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher (p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health.

IgA nephropathy recurs early in the graft when assessed by protocol biopsy.

BACKGROUND: The recurrence of IgA nephropathy (IgAN) in the allograft is common. Factors related to IgA recurrence are unclear. The aims of this study were to determine the incidence of IgAN recurrence as assessed by protocol biopsies and to identify predictive factors for recurrence. METHODS: We identified 65 protocol biopsies taken before the second year post-transplantation in patients with IgAN as primary renal disease. Diagnosis of recurrence of IgA was based on the detection of at least 1+ mesangial deposits of IgA. Pathological findings and clinical characteristics were retrospectively compared between recurrent and non-recurrent cases. RESULTS: IgAN recurrence rate was 32%. Mesangial C3 was detected in 83% of recurrent cases versus 17% in non-recurrent patients (P < 0.001). Normal urinalysis was observed in 52%. Non-recurrent patients had arteriolar hyalinosis in 31% of the cases versus none in IgAN recurrence (P = 0.006). Seventy-nine per cent of cyclosporine users were free of recurrence, whereas 45% of the patients without cyclosporine experienced recurrence (P = 0.03). The odds ratio (OR) for IgAN recurrence in patients using cyclosporine was 0.3 (confidence interval 0.1-0.9). Zero HLA-DR mismatch was associated with non-recurrence (P < 0.01). The OR for IgA recurrence was 6.7 if any degree of DR mismatch was present. IgAN recurrent patients had better glomerular filtration rate, but after censoring delayed graft function, the differences disappeared. Graft loss due to IgA recurrence was only 3%. CONCLUSIONS: IgAN recurrence rate was 32%. The histological diagnosis was not accompanied by abnormalities in the urinalysis in one-half of the patients. Full DR match and cyclosporine were associated with non-recurrence.

Recurrence and Visual Outcomes of Phototherapeutic Keratectomy in Lattice Corneal Dystrophy: A Cohort Study.

PURPOSE: To evaluate recurrence and visual outcomes of phototherapeutic keratectomy (PTK) in lattice corneal dystrophy. METHODS: Kaplan-Meier survival analyses were retrospectively performed. Recurrence was defined as central biomicroscopic findings of recurrence with decreased visual acuity: loss of at least two lines or visual acuity ≤ 20/40) at any time during the follow-up. RESULTS: Twenty-two virgin eyes and 10 with previous keratoplasty (20 patients; 13 women and 7 men) were studied during a mean of 4.7 ± 3.5 years (range: 11 months to 18 years). One and 5 years after the first PTK (PTK1), 1 of 32 and 12 of 32 eyes, respectively, recurred. The cumulative probabilities of recurrence were 3%, 48%, and 89% in the whole sample at 1, 5, and 10 years, respectively. All cases in the virgin group and 8 eyes in the previous keratoplasty group improved their visual acuity. There were no significant differences in recurrence probability between groups (log-rank test; P = .86). A second PTK (PTK2) was performed in 15 of 32 eyes, with 6 postoperative recurrences recorded. The cumulative probabilities of recurrence in the whole sample were 18%, 30%, and 44% at 1, 3, and 5 years, respectively. Visual acuity improved in 11 of 13 eyes in the virgin group and 2 of 2 eyes in the previous keratoplasty group. Recurrence probability after PTK1 and PTK2 was similar in the whole sample (log-rank test; P = .637). Persistent graft edema after PTK1 in one eye was the only complication found. CONCLUSIONS: PTK can be an effective, safe, and repeatable treatment to delay keratoplasty in symptomatic lattice corneal dystrophy. [J Refract Surg. 2022;38(1):43-49.].

Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy.

BACKGROUND: There is a lack of new therapeutic strategies for IgA nephropathy. Low-dose sirolimus inhibits mesangial cell proliferation and renal fibrosis in animal models. METHODS: We performed a pilot, randomized controlled trial to evaluate the efficacy and safety of low-dose sirolimus in patients with a high-risk IgA nephropathy. Twenty-three patients with a glomerular filtration rate (GFR) within 30-60 mL/min and/or proteinuria >1 g/day were randomly assigned to low-dose sirolimus plus enalapril and atorvastatin (SRL group, n = 14) or enalapril plus atorvastatin (CONTROL group, n = 9). Primary composite end point was variation of haematuria, proteinuria and blood pressure. Secondary end points were isotopic GFR, renal histology evaluated by Oxford classification and safety parameters evaluated at 6 and 12 months. RESULTS: Primary end point improved significantly in the SRL group at 12 months. Regarding isotopic GFR, patients included in the CONTROL group lost 8 mL/min/1.73 m(2), whereas those in the SRL arm improved 5 mL/min/1.73 m(2) (P = 0.03). Proteinuria decreased similarly in both study groups. At 1 year, SRL treatment was associated with a significant reduction of mesangial and endocapillary proliferation, whereas glomerular sclerosis, tubular atrophy and interstitial fibrosis were similar. Sirolimus was well tolerated; all patients remained on therapy at 12 months. CONCLUSION: The addition of low-dose sirolimus to enalapril and statin is safe, stabilizes renal function and reduces glomerular proliferative lesions in patients with poor prognosis IgA nephropathy.

Evaluation of a novel rapid genomic test including polygenic risk scores for the diagnosis and management of familial hypercholesterolaemia.

Introduction: Familial hypercholesterolaemia (FH) is a common autosomal dominant genetic condition, characterised by elevated LDL cholesterol (LDL-C), leading to premature cardiovascular disease (CVD). Early and accurate diagnosis, with implementation of preventative therapies, has a major impact on reducing premature CVD, morbidity and mortality. Genetic testing is recommended to confirm clinical diagnosis in the proband and enable cascade testing in relatives. There is growing evidence that the risk of CVD conferred by hypercholesterolaemia depends not only on monogenic causes but also on polygenic factors. GENinCode has developed a novel genomic testing system (Lipid inCode®) which we have assessed against an accredited National Health Service (NHS UK) genetic screening service in order to validate its diagnostic and clinical utility. Methods: DNA samples from 40 index cases who had been referred for FH testing in an ISO15189-accredited NHS genetic screening service, were retrospectively tested using the Lipid inCode® assay. The results were compared with those from NHS testing. Results: There was absolute concordance in variant detection between both diagnostic tests for monogenic and polygenic FH, the only difference being in the interpretation and classification of DNA variants based on ACMG guidelines, which did not differ by more than one classification class.  The Lipid inCode® test was equivalent to the NHS test in providing comprehensive genetic analysis that included the assessment of both monogenic (FH) and polygenic determinants of blood cholesterol and including a pharmacogenomic assessment of predisposition to statin-related myopathy. Conclusion: The Lipid inCode® diagnostic test can be undertaken with rapid turnaround and gave the same results as those reported by standard NHS genetic laboratory testing. In addition to assessment of monogenic FH, the Lipid inCode® assay provides additional genetic data, such as polygenic factors contributing to hypercholesterolaemia, a polygenic risk score (PRS) for coronary artery disease (CAD), pharmacogenomic testing for statin myopathy, and genetic predisposition to raised Lp(a).

Prevention of Recurrent Acute Otitis Media in Children Through the Use of Lactobacillus salivarius PS7, a Target-Specific Probiotic Strain.

Acute otitis media (AOM) is one of the most common bacterial infections in children. Empiric antibiotherapy leads to increasing antimicrobial resistance rates among otopathogens and may impair the correct development of the microbiota in early life. In this context, probiotics seem to be an attractive approach for preventing recurrent AOM (rAOM) through the restoration of the middle ear and nasopharyngeal microbiota. The aim of this study was the selection of a probiotic strain (Lactobacillus salivarius PS7), specifically tailored for its antagonism against otopathogens. Since L. salivarius PS7 was safe and displayed a strong antimicrobial activity against otopathogens, its efficacy in preventing rAOM was assessed in a trial involving 61 children suffering from rAOM. Children consumed daily ~1 × 108 CFU of L. salivarius PS7, and the number of AOM episodes were registered and compared with that observed in the previous 6 and 12 months. The microbiota of samples collected from the external auditory canal samples was quantitatively and qualitatively assessed. The number of AOM episodes during the intervention period decreased significantly (84%) when compared to that reported during the 6 months period before the probiotic intervention. In conclusion, L. salivarius PS7 is a promising strain for the prevention of rAOM in infants and children.

Chronic Kidney Disease is associated with an increase of Intimal Dendritic cells in a comparative autopsy study.

BACKGROUND: Chronic Kidney Disease (CKD) and inflammation are risk factors for atherosclerotic vascular disease (ASVD). In inflammatory conditions, Nuclear Factor-κB (NF-κB) is frequently activated and it has been detected in human ASVD. In this work, we investigated if the degree of inflammation and of NF-κB activation were increased in the aorta of patients with CKD. METHODS: This is a case-control pilot study performed on 30 abdominal aorta samples from 10 human autopsies. Cases were patients with CKD and controls patients with normal glomerular filtration rate (eGFR). Infiltrating mononuclear cells (S100(+), CD3(+), CD40(+), CD40L(+)) and activation of NF-κB were identified by immunohistochemistry. FINDINGS: The number of cells in the intima which showed activated nuclear NF-κB correlated with severity of ASVD lesions (r = 0.56, p = 0.003), with numbers of CD3(+) lymphocytes in adventitia (r = 0.50, p = 0.008), with numbers of CD40(+) cells in the intima (r = 0.59, p = 0.002) or in the adventitia (r = 0.45, p = 0.02), and with numbers of CD40L(+) cells in the intima (r = 0.51, p = 0.011). Increased numbers of S100+ Intimal Dendritic cells (IDCs) were associated with ASVD (p = 0.03) and CKD (p = 0.01). CONCLUSIONS: Number of CD3(+) cells, of CD40(+) cells, of CD40L(+) cells and the degree of NF-κB activation were increased in ASVD lesions suggesting a role for the adaptive T cell in the development of ASVD lesions. IDCs were associated both with ASVD and CKD suggesting a role of these cells in the pathogenesis of ASVD in CKD.

International variation in histologic grading is large, and persistent feedback does not improve reproducibility.

Histologic grading systems are used to guide diagnosis, therapy, and audit on an international basis. The reproducibility of grading systems is usually tested within small groups of pathologists who have previously worked or trained together. This may underestimate the international variation of scoring systems. We therefore evaluated the reproducibility of an established system, the Banff classification of renal allograft pathology, throughout Europe. We also sought to improve reproducibility by providing individual feedback after each of 14 small groups of cases. Kappa values for all features studied were lower than any previously published, confirming that international variation is greater than interobserver variation as previously assessed. A prolonged attempt to improve reproducibility, using numeric or graphical feedback, failed to produce any detectable improvement. We then asked participants to grade selected photographs, to eliminate variation induced by pathologists viewing different areas of the slide. This produced improved kappa values only for some features. Improvement was influenced by the nature of the grade definitions. Definitions based on "area affected" by a process were not improved. The results indicate the danger of basing decisions on grading systems that may be applied very differently in different institutions.

Mycophenolate mofetil reduces deterioration of renal function in patients with chronic allograft nephropathy. A follow-up study by the Spanish Cooperative Study Group of Chronic Allograft Nephropathy.

BACKGROUND: Although studies have shown that mycophenolate mofetil (MMF) with cyclosporine (CsA) and prednisone can reduce the incidence of acute rejection and increase the half-life of the graft, the effects of MMF on established chronic allograft nephropathy (CAN) are controversial. METHODS: We studied 121 patients with biopsy-proven CAN, 59 treated with CsA and prednisone and 62 treated with triple-drug therapy with azathioprine. At inclusion, each group received 2 g per day of MMF and azathioprine was stopped. Renal function was measured by the glomerular filtration rate (GFR) obtained by creatinine clearance (Cockcroft-Gault) and monitored by the slope of the GFR, adjusted using linear regression. RESULTS: The median follow-up, after incorporation of MMF, was 36 (13-36) months, with 103 (85.1%) having a full 3-year follow-up. Before the introduction of MMF, there was progressive deterioration in renal function (GFR: 54.8+/-20.9 vs. 39.7+/-14.0 mL/min, P<0.001). After introduction of MMF, renal function remained stable (GFR: 39.7+/-14.0 vs. 41.3+/-10.8 mL/min, P=NS), with a significant change in the slope of the GFR (-0.0144 vs. +0.00045, P<0.001). In 65 patients in whom CsA blood levels remained unchanged during follow-up (148.0+/-65.6 vs. 154.1+/-58.2, P=NS), the slope of the GFR showed a reduction in loss of renal function (-0.0147 vs. -0.0001, P<0.001). CONCLUSIONS: Treatment with MMF reduced the progressive deterioration of renal function in patients with CAN, independently of the blood levels of CsA.

Baseline immunosuppression is associated with histological findings in early protocol biopsies.

BACKGROUND: Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions that have been related with graft outcome. However, the utility of protocol biopsies to manage baseline immunosuppression has not been well characterized. METHODS: We performed a case-control study to compare histological lesions observed in protocol biopsies in 49 patients treated with tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisone to 49 patients treated with cyclosporine Neoral (CsA), MMF, and prednisone. Histological lesions were graded according to 1997 Banff criteria. The analysis was done according to an intention-to-treat basis. RESULTS: Patients treated with TAC displayed in the protocol biopsy a lower acute score (0.61+/-1.01 vs. 1.26+/-1.45; P=0.0115) and a similar chronic score (1.57+/-1.97 vs. 1.51+/-1.59; P=NS). Transplant glomerulopathy was also lower in TAC treated patients (0.02+/-0.14 vs. 0.20+/-0.41; P=0.0037). Univariate and multivariate logistic regression analysis showed that the presence of acute inflammation was associated with tacrolimus treatment (relative risk [RR]: 0.30, 95% confidence interval [CI]: 0.11-0.84; P=0.0211) and the time of biopsy (RR per month: 0.56, 95% CI: 0.32-0.97; P=0.0394). The presence of chronic lesions was only associated with serum creatinine at the time of biopsy (RR: 1.01, 95% CI: 1.00-1.02; P=0.0439). CONCLUSIONS: The incidence of inflammatory lesions and transplant glomerulopathy is lower in patients treated with TAC than in patients treated with CsA. These data suggest that baseline immunosuppression could influence the severity of histological lesions in stable grafts.

Goodpasture syndrome during the course of a Schönlein-Henoch purpura.

Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old patient presented with Schönlein-Henoch purpura with kidney involvement followed by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA antibodies led to the diagnosis of Goodpasture syndrome, which implies the possibility that the well-known pulmonary involvement during the course of Schönlein-Henoch purpura could be caused by Goodpasture syndrome in certain cases. In cases of glomerulonephropathy with lung involvement, clinicians should not limit their investigations to anti-GBM IgG.

A comparative genomic hybridization study in a 46,XX male.

OBJECTIVE: To identify Y chromosome material in an azoospermic male with an XX karyotype. DESIGN: Case report. SETTING: Faculty of medicine and Centro de Patologia Celular (CPC) medical center. PATIENT(S): A 33-year-old man with infertility. INTERVENTION(S): G-banding, fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and comparative genomic hybridization (CGH). MAIN OUTCOME MEASURE(S): FISH for X and Y chromosomes, PCR for the SRYgene and amelogenin gene in the Xp (AMGX) and (AMGY), and losses or gains with CGH. RESULT(S): FISH analysis using X and Y chromosome-specific probes showed an X chromosome containing Y chromosome sequences on the top of the short arm; this Y chromosome region was not visible by conventional cytogenetic analysis. PCR amplification of DNA showed the presence of the sex-determining region of the Y chromosome (SRY) and the amelogenin gene in the pseudoautosomal boundary of the X chromosome (AMGX). CGH confirmed the presence of the chromosome region Yp11.2-pter and detected the presence of the two otherwise normal X chromosomes. CONCLUSION(S): The two Xpter (XPAR1) pseudoautosomal regions present in this XX male suggest the need to reevaluate XX males using CGH and PCR to characterize the clinical variability in XX males due to genes other than those located on the Y chromosome.

Fatal bacillary angiomatosis mimicking an infiltrative vascular tumour in the immune restoration phase of an HIV-infected patient.

Bacillary angiomatosis mainly affects the HIV-infected population. Information is limited on the evolution of bacillary angiomatosis during immune restoration following initiation of HAART. We report an unusual case of fatal Bartonella quintana bacillary angiomatosis occurring in an HIV-infected man during the immune restoration phase.

Early subclinical rejection as a risk factor for late chronic humoral rejection.

BACKGROUND: Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause. MATERIALS AND METHODS: Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause. RESULTS: Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1-6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8-58.8; P=0.085) was associated with CHR. CONCLUSION: Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

Rapid aneuploidy testing versus traditional karyotyping in amniocentesis for certain referral indications.

OBJECTIVE: (1) To determine the suitability of replacing full karyotype analysis with quantitative fluorescent polymerase chain reaction (QF-PCR) for prenatal diagnosis in amniotic fluid samples obtained by amniocentesis. (2) To evaluate an indication-based classification of cases at risk of missing clinically relevant chromosomal disorders by QF-PCR. METHODS: We reviewed all fetal karyotypes obtained by amniocentesis between January 2004 and December 2008. We compared the cytogenetic findings obtained through conventional karyotype with those that would have been theoretically obtained using QF-PCR. RESULTS: Of the 4007 karyotypes obtained, 110 abnormal karyotypes were found (2.8%). Out of these, 30 (27%) were chromosomal abnormalities (CA) which would not have been detected by PCR alone. These included 16 cases (53%) predicted to confer no increased risk, 9 (30%) predicted to have a low risk, and 5 (17%) with an uncertain or high risk of fetal abnormality. A policy of QF-PCR alone would have identified 80 of 85 (94%) clinically significant CA. When QF-PCR shows a normal result, the overall residual risk is 0.75% for any CA and 0.12% for a clinical significant CA. CONCLUSION: In our population, a policy of QF-PCR alone would miss 0.12% clinically relevant CA. QF-PCR directed to common aneuploidies can be considered as an economically and clinically acceptable prenatal diagnosis policy, offering full karyotype only for specific indications.

Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates.

Exploring new immunosuppressive strategies inducing donor-specific hyporesponsiveness is an important challenge in transplantation. For this purpose, a careful immune monitoring and graft histology assessment is mandatory. Here, we report the results of a pilot study conducted in twenty renal transplant recipients, analyzing the immunomodulatory effects of a protocol based on induction therapy with rabbit anti-thymocyte globulin low doses, sirolimus, and mofetil mycophenolate. Evolution of donor-specific cellular and humoral alloimmune response, peripheral blood lymphocyte subsets and apoptosis was evaluated. Six-month protocol biopsies were performed to assess histological lesions and presence of FOXP3+ regulatory T cells (Tregs) in interstitial infiltrates. After transplantation, there was an early and transient apoptotic effect, mainly within the CD8+ HLADR+ T cells, combined with a sustained enhancement of CD4+ CD25(+high) lymphocytes in peripheral blood. The incidence of acute rejection was 35%, all steroid sensitive. Importantly, only pretransplant donor-specific cellular alloreactivity could discriminate patients at risk to develop acute rejection. Two thirds of the patients became donor-specific hyporesponders at 6 and 24 mo, and the achievement of this immunologic state was not abrogated by prior acute rejection episodes. Remarkably, donor-specific hyporesponders had the better renal function and less chronic renal damage. Donor-specific hyporesponsiveness was inhibited by depleting CD4+ CD25(+high) T cells, which showed donor-Ag specificity. FOXP3+ CD4+ CD25(+high) Tregs both in peripheral blood and in renal infiltrates were higher in donor-specific hyporesponders than in nonhyporesponders, suggesting that the recruitment of Tregs in the allograft plays an important role for renal acceptance. In conclusion, reaching donor-specific hyporesponsiveness is feasible after renal transplantation and associated with Treg recruitment in the graft.

A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies.

A series of 44 unrelated patients in whom COL2A1 screening demonstrated normal results but whose phenotype was nevertheless highly suggestive of either Stickler syndrome (with ocular involvement) or Marshall syndrome were investigated for mutations in the COL11A1 gene. Heterozygous COL11A1 mutations were found in 10 individuals. A splice site alteration (involving introns 47-55) was present in seven cases, with one in intron 50 (c.3816 + 1G > A) occurring in three patients. Two patients had a different deletion, and a missense mutation (Gly1471Asp) was observed in one case. In 4/10 patients the phenotype was classified as Marshall syndrome because of early-onset severe hearing loss and characteristic facial features. These four patients were all heterozygous for a splice site mutation in intron 50. One of these cases had a type 1 vitreous anomaly despite the presence of a COL11A1 mutation. The remaining 6/10 patients had an overlapping Marshall-Stickler phenotype with less pronounced facial features. None of these had a mutation in the hot spot region of intron 50.

Evaluation of pre-implantation kidney biopsies: comparison of Banff criteria to a morphometric approach.

BACKGROUND: Donor glomerulosclerosis, interstitial fibrosis, and fibrous intimal thickening correlate with graft outcome. We evaluate chronic lesions in donor biopsies according to Banff criteria and with a morphometric technique to ascertain their predictive value on graft outcome. METHODS: We evaluated 77 cadaveric donor biopsies according to Banff criteria. Glomerulosclerosis was expressed as the percentage of global sclerotic glomeruli. The following morphometric parameters were obtained: cortical interstitial volume fraction (Vvint/c), cortical glomerular volume fraction (Vvglom/c), mean glomerular volume (Vg), mean and maximal intimal arterial volume fraction (Vvintima/art), and Vvintima/art of the largest artery. We evaluated the correlation of histologic lesions with delayed graft function, 3 months' glomerular filtration rate (GFR), and death-censored graft survival. RESULTS: Multivariate logistic regression showed that delayed graft function was associated with cv score [relative risk (RR) 4.2 and 95% CI 1.1 to 16.0) and glomerulosclerosis (RR 1.06 and 95% CI 1.01 to 1.13). Stepwise regression showed that Vvint/c and glomerulosclerosis were independent predictors of 3 months' GFR (R= 0.62, P= 0.0001). Repeated analysis not considering morphometric parameters showed that glomerulosclerosis, cv score and ci score were independent predictors of 3 months' GFR (R= 0.64, P= 0.0001). A donor chronic damage score was generated considering glomerulosclerosis, cv score and ci score. This score after adjusting for clinical variables was associated with 3 months' GFR (R= 0.71, P < 0.0001) and death-censored graft survival (RR 2.2 and 95% CI 1.3 to 3.7). CONCLUSION: Combined evaluation of donor glomerulosclerosis, chronic vascular and interstitial damage according to Banff criteria allows a precise prediction of graft outcome. Morphometric evaluation of donor biopsies does not improve the predictive value of semiquantitative grading.

Resistive index and chronic allograft nephropathy evaluated in protocol biopsies as predictors of graft outcome.

INTRODUCTION: The presence of chronic allograft nephropathy (CAN) in protocol biopsies is negatively associated with graft survival. Although recent studies have indicated that the resistive index (RI) is a predictor of graft failure, it does not correlate with CAN in stable grafts. We therefore studied the relationship between RI and CAN and examined the predictive value of both parameters on graft outcome. METHODS: Included were patients transplanted between 1997 and 2002 and who had protocol biopsies and RI determinations. Renal lesions were blindly evaluated according to Banff 97 criteria. Mean glomerular volume, cortical interstitial volume fraction and intimal arterial volume fraction were estimated using a point counting technique. RI was determined before biopsy in at least two different renal locations. The outcome variable was defined as graft failure or a 30% serum creatinine increase between protocol biopsy and last follow-up. RESULTS: Eighty-seven patients were included. RI correlated with recipient age (R = 0.52, P < 0.0001), diastolic blood pressure (R = -0.36, P = 0.0006), pulse pressure index (R = 0.27, P = 0.009) and g-score for histological glomerulitis (rho = 0.30, P = 0.0054), but there were no correlations between RI and chronic Banff scores or any morphometric parameter. The presence of CAN (relative risk, 3.5; 95% confidence interval 1.2-10.2; P = 0.02) but not RI was associated with the outcome variable. CONCLUSION: RI was associated with surrogate measures of vascular compliance such as recipient age and pulse pressure index but not with chronic allograft damage, even when it was evaluated by histomorphometry. Our results indicate that histology may be superior to RI in predicting graft function deterioration, at least in patients with stable renal function.