The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

Systematic review: hepatitis C viraemic allografts to hepatitis C-negative recipients in solid organ transplantation.

BACKGROUND: Given the success of direct-acting antivirals (DAAs) in treating hepatitis C (HCV), interest is growing in utilizing solid organs from allografts with active HCV to expand donor availability. AIM: To review post-transplant outcomes and patient survival in HCV-negative recipients receiving solid organ transplants (SOT) from viraemic, that is, HCV+/NAT+ (nucleic acid testing) allografts. METHODS: A literature search was conducted on PubMed and EMBASE from 01/01/2007 to 4/17/2021 for articles matching eligibility criteria. Two authors independently screened titles and abstracts. Disagreements were solved by a third independent reviewer. Methodological quality assessment was done using a modified Newcastle-Ottawa scale (NOS). Data synthesis was done qualitatively using median, ranges and percentages. RESULTS: Thirty-five studies were included (or 852 SOTs): 343 kidney, 233 heart, 204 liver, and 72 lung transplants from viraemic allografts. Of the recipients eligible for sustained virological response at 12 weeks (SVR12) calculation, 100% achieved cure from HCV. No deaths/graft failures were reported to be related to HCV transmission. Seven SOT recipients had viral relapse, with all seven patients treated successfully. Four patients developed fibrosing cholestatic hepatitis with complete resolution post-treatment. CONCLUSIONS: Transplanting viraemic organs into uninfected individuals can become the standard of care for patients who do not have contraindications to DAAs.

Outcomes of Deceased Donor Kidney Transplantation Using Expanded Criteria Donor Kidneys Following Pulsatile Preservation.

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

The Abdominal Transplant Surgery Workforce: Current state and future trends.

Transplant surgical workforce concerns have arisen in the last 5 years as reflected in challenges securing job opportunities for new fellows. The present survey was designed by the ASTS Membership and Workforce Committee to describe the current practice characteristics of transplant centers in order to estimate changes in the workforce. The survey questionnaire requested information about the transplant programs, the transplant surgeons involved in the program, and the estimated changes in the staffing of the program over the next 3 years. Seventy-one transplant centers responded from a total of 235 identified and queried (30.2% response rate), with median responding centers per UNOS region of 7 (IQR 4.5-8.5). The recruitment outlook for the next 3 years forecasts a positive inflow of surgeons at a 2:1 rate (incoming:leaving). The new female transplant workforce within the responding cohort has increased from 3.7% in 1980 to 18.4% in 2010. Currently, 13.1% of practicing US transplant surgeons in this survey are female which is higher than many other surgical specialties. This report represents the most up-to-date view into the abdominal transplant surgical workforce. The positive job recruitment outlook for transplant surgeons and the narrowing gender gap are new findings from this study.

The development of practice guidelines for independent living donor advocates.

The practice recommendations discussed here are based on the findings of the national survey as well as the opinions of the authors. The recommendations that are proposed here are not exhaustive and are aspirational in intent and are likely to evolve with time. Practice guidelines are recommended for legal and regulatory issues (e.g., state or federal laws), consumer or public benefit (e.g., improving service delivery, avoiding harm to the patient, decreasing disparities in underserved or vulnerable populations), and for professional guidance (e.g., new role, professional risk management issues, advances in practice). Without such practice guidelines, donors, and indirectly the candidates, may be at increased risk for possible bias or undue harm.

Prevention of poor psychosocial outcomes in living organ donors: from description to theory-driven intervention development and initial feasibility testing.

CONTEXT: Although some living donors experience psychological, somatic, and interpersonal difficulties after donation, interventions to prevent such outcomes have not been developed or evaluated. OBJECTIVE: To (1) summarize empirical evidence on psychosocial outcomes after donation, (2) describe a theoretical framework to guide development of an intervention to prevent poor outcomes, and (3) describe development and initial evaluation of feasibility and acceptability of the intervention. METHODS: Based on a narrative literature review suggesting that individuals ambivalent about donation are at risk for poor psychosocial outcomes after donation, the intervention targeted this risk factor. Intervention structure and content drew on motivational interviewing principles in order to assist prospective donors to resolve ambivalence. Data were collected on donors' characteristics at our institution to determine whether they constituted a representative population in which to evaluate the intervention. Study participants were then recruited to assess the feasibility and acceptability of the intervention. They were required to have scores greater than 0 on the Simmons Ambivalence Scale (indicating at least some ambivalence about donation). RESULTS: Our population was similar to the national living donor population on most demographic and donation-related characteristics. Eight individuals who had been approved to donate either a kidney or liver segment were enrolled for pilot testing of the intervention. All successfully completed the 2-session telephone-based intervention before scheduled donation surgery. Participants' ratings of acceptability and satisfaction were high. Open-ended comments indicated that the intervention addressed participants' thoughts and concerns about the decision to donate. CONCLUSIONS: The intervention is feasible, acceptable, and appears relevant to donor concerns. A clinical trial to evaluate the efficacy of the intervention is warranted.

Rates and correlates of health maintenance behaviors after living kidney donation.

CONTEXT AND OBJECTIVE: Donating a kidney may provide an opportunity for donors to reevaluate their health maintenance behaviors (eg, regular exercise, smoking cessation, medical checkups). Although the effect of donation on donors' health, quality of life, and financial outcomes has received growing attention, no studies have examined whether donation is related to changes in health maintenance behaviors. The study aims were to (1) describe and compare kidney donors' health maintenance behaviors before and after donation, and (2) determine the correlates of health maintenance behaviors after donation. DESIGN, SETTING, PARTICIPANTS AND MEASURES: We conducted a telephone-interview study with 85 randomly selected laparoscopic kidney donors in a major US transplant center to assess health behaviors before and after donation, postdonation characteristics (eg, quality of life, postsurgical pain), and demographics. RESULTS: Sample demographics included a median age of 48 years; 55% were female, 82% were white, 71% were married, and 52% were college graduates. Few health behaviors changed significantly from before to after donation. Only the rate of medical checkups increased after donation (P< .001). Logistic regression was used to examine the association of demographics and postdonation characteristics with postdonation health maintenance behaviors, after adjusting for predonation behavior. Older age, higher income, less postsurgical pain, and better physical functioning were associated with more exercise after donation. Longer time since donation was associated with a higher prevalence of obesity. CONCLUSIONS: These results may help identify donors who are at greater risk for poor health maintenance behaviors after donation and suggest areas of health behavior that should be the focus of education sessions before donation.

Putative episodes of T-cell-mediated rejection in patients with sustained BK viruria but no viremia.

BACKGROUND: Polyomavirus BK (BKV) infection characterized by viruria alone is considered to be of little clinical significance, but this issue has not been systematically studied. METHODS: We studied 230 patients with sustained viruria from whom multiple samples taken after a median of 877 days (range, 24-2739) showed no progression to viremia or nephropathy. Biopsies satisfying Banff thresholds for inflammation and tubulitis in the presence of viruria but negative for BKV stains were designated as putative T-cell-mediated acute rejection. RESULTS: Compared with no viruria (n=515), sustained viruria was associated with more putative rejection episodes (0.62 vs. 0.33 per patient, P=0.006) and greater incidence of steroid resistance (36.2% vs. 19.6%, P=0.002). Most putative rejection episodes (52.1%) occurred concurrently with viruria, with a minority before (7.8%) or after (40.1%) BKV clearance. Steroid resistance was more frequent in putative rejection with concurrent viruria (48.6%), compared with rejection before (9.1%) or after (26.0%) viral clearance. These observations remained valid even on a separate analysis of patients with BKV load 1E+07 copies per mL or less. As assessed by the slope of reciprocal serum creatinine levels, accelerated deterioration of graft function resulted from rejection episodes occurring more than 2 years after transplantation. CONCLUSIONS: These observations indicate that intrarenal viral replication in sustained viruria is frequently associated with putative acute rejection. The implications of this association on the development of immune tolerance deserve further investigation.

Antibody-mediated rejection in kidney transplantation: a review.

Antibody mediated rejection (AMR) poses a significant and continued challenge for long term graft survival in kidney transplantation. However, in the recent years, there has emerged an increased understanding of the varied manifestations of the antibody mediated processes in kidney transplantation. In this article, we briefly discuss the various histopathological and clinical manifestations of AMRs, along with describing the techniques and methods which have made it easier to define and diagnose these rejections. We also review the emerging issues of C4d negative AMR, its significance in long term allograft survival and provide a brief summary of the current management strategies for managing AMRs in kidney transplantation.

Long-term effects of alemtuzumab on regulatory and memory T-cell subsets in kidney transplantation.

BACKGROUND: Induction with lymphocyte-depleting antibodies is routinely used to prevent rejection but often skews T cells toward memory. It is not fully understood which memory and regulatory T-cell subsets are most affected and how they relate to clinical outcomes. METHODS: We analyzed T cells from 57 living-donor renal transplant recipients (12 reactive and 45 quiescent) 2.8±1.4 years after alemtuzumab induction. Thirty-four healthy subjects and nine patients with acute cellular rejection (ACR) were also studied. RESULTS: We found that alemtuzumab caused protracted CD4 more than CD8 T-lymphocyte deficiency, increased proportion of CD4 memory T cells, and decreased proportion of CD4 regulatory T cells. Reactive patients exhibited higher proportions of CD4 effector memory T cells (TEM) and CD8 terminally differentiated TEM (TEMRA), with greater CD4 TEM and CD8 TEMRA to regulatory T cell ratios, than quiescent patients or healthy controls. Patients with ongoing ACR had profound reduction in circulating CD8 TEMRA. Mixed lymphocyte assays showed significantly lower T-cell proliferation to donor than third-party antigens in the quiescent group, while reactive and ACR patients exhibited increased effector molecules in CD8 T cells. CONCLUSIONS: Our findings provide evidence that T-cell skewing toward TEM may be associated with antigraft reactivity long after lymphodepletion. Further testing of TEM and TEMRA subsets as rejection predictors is warranted.

Immunohistochemical markers of tissue injury in biopsies with transplant glomerulitis.

Transplant glomerulitis is associated with suboptimal graft function. To understand its pathogenesis and to assess the parameters of potential prognostic value, we immunostained 25 paraffin-embedded allograft biopsies showing glomerulitis for markers of complement activation (C4d), cytotoxicity (Granzyme-B), apoptosis (Bcl-XL, Bcl-2, and Fas-L), and endothelial injury (von Willebrand factor). Staining was semiquantitatively assessed in different anatomical compartments, and comparison was made with 40 control allograft biopsies without glomerulitis. Biopsies with glomerulitis had more frequent incidence of "mixed" T-cell and antibody-mediated rejection compared with controls [8/25 (32%) versus 4/40 (10%), P = .046]. Furthermore, they had higher glomerular capillary-C4d scores (1.9 ± 1.1 versus 1.2 ± 1.2, P = .015), which tended to persist when biopsies showing transplant glomerulopathy were excluded. Higher glomerular capillary-C4d scores were observed in samples with versus without donor-specific antibody (2.5 ± 0.9 versus 1.2 ± 1.2, P = .01). Compared with controls, biopsies with glomerulitis had more intraglomerular (4.8 ± 4.5 versus 0.9± 0.8 cells/glomerulus, P < .001) and interstitial mainly peritubular capillary (6.1 ± 4.1 versus 3.2 ± 3.4 cells/hpf, P = .002) Granzyme-B(+) leukocytes. Higher mesangial-von Willebrand factor scores were noted in the glomerulitis group (1.8 ± 1.0 versus 0.8 ± 0.8, P = .003) and correlated with the percentage of inflamed glomeruli (r = 0.54, P < .001). Interstitial-von Willebrand factor was associated with a higher peritubular capillaritis score (interstitial-von Willebrand factor: 1.6 ± 1.2 versus no interstitial-von Willebrand factor: 0.6 ± 0.9, P = .02). Glomerular capillary-Bcl-XL was not associated with accommodation. Finally, no difference in Bcl-2 or Fas-L was observed upon comparing glomerulitis to controls. In conclusion, glomerular injury in transplant glomerulitis appears to be mediated by complement activation and cellular cytotoxicity. Mesangial- or interstitial-von Willebrand factor identified cases with more severe microcirculation injury.

Outcomes of renal transplantation in recipients with peak panel reactive antibody >30% under tacrolimus-based immunosuppression.

BACKGROUND: Renal transplant recipients with high panel reactive antibodies (PRA) have worse outcomes than those with lower PRA. High PRA re-transplant recipients are thought to have worse outcomes than high PRA first transplant recipients. In this study, we examined outcomes of renal transplantation recipients with a peak PRA >30% and compared the outcomes of first and re-transplanted recipients. MATERIAL/METHODS: Survival outcomes between recipients of first transplants (n=68) and re-transplants (n=155) operated between June 1990 and August 2000 were compared. Sub-group analysis was done based on patient's gender, race and first/re-transplant. All patients received tacrolimus-based immunosuppression. RESULTS: No difference in graft survival was noted between first and re-transplanted patients. Ten-year patient survival was better in the re-transplanted group (p<0.004). Factors affecting patient survival on univariate analysis were age >55 years (p=0.015), deceased donor transplant (p=0.009), first transplant patient (p=0.004) and diabetes mellitus (DM) as the cause of End Stage Renal Disease (ESRD) (p=0.005). On multivariable analysis, factors affecting patient survival were number of the transplant (re-transplant versus first transplant, Relative risk [RR]=0.54, p=0.009) and cause of ESRD (DM versus no DM, RR=1.91, p=0.012).Diabetes as a cause for ESRD was the only factor affecting graft survival on univariate(p=0.015) and multivariable analysis (DM versus no DM, RR=1.63, p=0.017). CONCLUSIONS: High PRA recipients of first transplants had poorer patient survival than high PRA re-transplants. On multivariable analysis, diabetes etiology of ESRD and first transplantation were found to be independent risk factors for poorer patient survival.

Allospecific CD154+ T-cytotoxic memory cells identify recipients experiencing acute cellular rejection after renal transplantation.

BACKGROUND: The novel, recently described allo (antigen)-specific CD154+T cells were evaluated for their association with acute cellular rejection (ACR) in 43 adult renal transplant recipients receiving steroid-free tacrolimus after alemtuzumab induction. METHODS: Single blood samples corresponding to "for cause" allograft biopsies were assayed for CD154+naive or memory T-helper or T-cytotoxic cells in 16-hr mixed leukocyte reaction. RESULTS: Intra- and interassay variation was less than 10% for a variety of conditions. In logistic regression, leave-one-out cross-validation, and receiver-operating characteristic analyses, the rejection-risk threshold of allospecific CD154+T-cytotoxic memory cells (TcMs) associated best with biopsy-proven ACR with a sensitivity/specificity of 88% in 32 of 43 subjects. Sensitivity/specificity of 100%/88% was replicated in blinded prediction in the remaining 11 subjects. Allospecific CD154+TcM correlated inversely with CTLA4+TcM (Spearman r=-0.358, P=0.029) and increased significantly with increasing histological severity of ACR (P=2.99E-05, Kruskall-Wallis). CONCLUSIONS: The strong association between ACR and allospecific CD154+TcM may be useful in minimizing protocol biopsies among recipients at reduced rejection risk.

Kidney transplantation at the University of Pittsburgh.

As with other similar-sized programs across the country, kidney transplantation has evolved at the University of Pittsburgh. The shortage of organs represents the biggest problem, and in response there has been an increase in the number of live-donor and extended-criteria-donor transplants. Laparoscopic nephrectomy techniques have been widely used at our center with live donors, and have had a significant impact on the number of live-donor transplants. As the program has matured, we have seen an increasing number of recipients needing re-transplantation and patients with non-renal transplants who have progressed to ESRD and need a kidney transplant. This fact highlights the second major problem facing the field today: the morbidity associated with long-term immunosupression. Our program, along with others, continues to look at methods to minimize the overall amount of long-term immunosuppression to which patients are exposed.

HMG-CoA reductase inhibitors in kidney transplant recipients receiving tacrolimus: statins not associated with improved patient or graft survival.

BACKGROUND: The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival. METHODS: We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival. RESULTS: 36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models. CONCLUSIONS: In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.

Kidney after nonrenal transplantation-the impact of alemtuzumab induction.

BACKGROUND: Calcineurin inhibitor nephrotoxicity in nonrenal allograft recipients can lead to end-stage renal disease and the need for kidney transplantation. We sought to evaluate the role of alemtuzumab induction in this population. PATIENTS AND METHODS: We evaluated 144 patients undergoing kidney transplantation after nonrenal transplantation between May 18, 1998, and October 8, 2007. Seventy-two patients transplanted between January 15, 2003, and October 8, 2007, received alemtuzumab induction and continued their pretransplant immunosuppression. Seventy-two patients transplanted between May 18, 1998, and July 21, 2007, did not receive alemtuzumab induction, but received additional steroids and maintenance immunosuppression. Donor and recipient demographics were comparable. RESULTS: Overall, 1- and 3-year patient survival and renal function were comparable between the two groups. One- and 3-year graft survival was 93.0% and 75.3% in the alemtuzumab group and 83.3% and 68.7% in the no alemtuzumab group, respectively (P=0.051). The incidence of acute rejection was lower in the alemtuzumab group, 15.3%, than in the no alemtuzumab group, 41.7% (P=0.0001). The incidence of delayed graft function was lower in the alemtuzumab group, 9.7%, than in the no alemtuzumab group, 25.0% (P=0.003). The incidence of viral complications was comparable. CONCLUSION: Alemtuzumab induction with simple resumption of baseline immunosuppression in patients undergoing kidney transplantation after nonrenal transplantation represents a reasonable immunosuppressive strategy.

The significance of renal C4d staining in patients with BK viruria, viremia, and nephropathy.

Peritubular capillary C4d staining in allograft kidney is an important criterion for antibody-mediated rejection. Whether BK virus infection can result in complement activation is not known. We studied 113 renal allograft biopsies from 52 recipients with a history of BK virus activation. The samples were classified into four groups according to the concurrent detection of BK virus DNA in urine, plasma, and/or biopsy: BK-negative (n=37), viruria (n=53), viremia (n=7), and nephropathy (n=16) groups. The histological semiquantitative peritubular capillary C4d scores in the viremia (0.3+/-0.8) and BK nephropathy (0.6+/-0.9) groups were lower than those in the BK-negative group (1.2+/-1.1, P=0.05 and P=0.06, respectively) and the viruria group (1.2+/-1.1, P=0.04 and P=0.06, respectively). Diffuse or focal peritubular capillary C4d staining was present in 9/76 (12%) and 14/76 (19%) of all samples with concurrent BK virus reactivation (viruria, viremia, and nephropathy). The diagnosis of antibody-mediated rejection could be established in 7/9 (78%) and 5/14 (36%) of these samples, respectively. Diffuse tubular basement membrane C4d staining was restricted to BK nephropathy cases (4/16, 25%). Semiquantitative tubular basement membrane C4d scores were higher in BK nephropathy (1.2+/-1.3) compared with BK-negative (0.05+/-0.3, P=0.017) and viruria (0.0+/-0.0, P=0.008) groups. Bowman's capsule C4d staining was more frequent in BK nephropathy (5/16) compared with the aforementioned groups (2/36 (P=0.023) and 4/51 (P=0.03), respectively). Within the BK nephropathy group, samples with tubular basement membrane stain had more infected tubular epithelial cells (12.1+/-7.6% vs 4.4+/-5.0%, P=0.03) and a trend toward higher interstitial inflammation scores. In conclusion, peritubular capillary C4d staining remains a valid marker for the diagnosis of antibody-mediated rejection in the presence of concurrent BK virus infection. A subset of biopsies with BK nephropathy shows tubular basement membrane C4d staining, which correlates with marked viral cytopathic effect.

Clinicopathologic analysis of patients with BK viruria and rejection-like graft dysfunction.

BK virus infection can be associated with interstitial inflammation, tubulitis without viral cytopathic effect, and negative in situ hybridization for viral DNA. We evaluated the consequences of increased immunosuppression in 32 viruric patients, with such acute cellular rejection-like changes in allograft biopsies (n = 50). When follow-up information was available, complete creatinine response, decrease in urine viral load (VL), and improvement in overall Banff grade for acute rejection were only seen in 13 (27%) of 49, 7 (21%) of 33, and 10 (39%) of 26 episodes of graft dysfunction, respectively. Histologic response was not always accompanied by clinical response. This low rate of response to antirejection therapy suggests that interstitial nephritis in a subset of these patients was secondary to viral infection. The presence of high VL (>1.0 E+05 copies/mL) was associated with low immune cell function values (129 +/- 99 ng of adenosine triphosphate per milliliter, P = .08) and with significant development of viremia after antirejection treatment (5/9 [56%] versus 0/24 [0%] in patients with low VL, P < .001).

Neutrophilic tubulitis as a marker for urinary tract infection in renal allograft biopsies with C4d deposition.

BACKGROUND: Neutrophilic tubulitis accompanied by intratubular neutrophil clusters in the renal allograft is a surrogate marker for urinary tract infection (UTI). Overlapping histologic findings can occur in antibody-mediated rejection, which is characterized by peritubular capillary (PTC) deposition of C4d. This study evaluated the incidence of UTI in biopsies with concurrent neutrophilic tubulitis and PTC C4d staining. METHODS: Thirty-three allograft biopsies from 27 patients selected for the presence of simultaneous C4d staining and neutrophilic tubulitis were correlated with urine culture (U/C) results. RESULTS: U/C obtained on the same day as the biopsy confirmed UTI in 13 of 33 (39%) biopsies. Among 20 patients with negative U/C; prior culture results within 10 days of the biopsy were available for nine patients, and 5 of 9 (55%) were positive. Thus, UTI was confirmed in 18 of 33 (54%) biopsies. Biopsy interpretation and clinical management was confounded by changes of concurrent acute cellular rejection and antibody-mediated rejection confirmed by demonstration of donor-specific antibodies. Combined therapy with antibiotics and antirejection medications (ART) was administered to 12 of 18 (67%) patients. CONCLUSIONS: Neutrophilic tubulitis accompanied by neutrophil clusters in the tubular lumen is a useful marker of UTI, even in the presence of PTC C4d deposition. Therapeutic response to antibiotics is limited by co-existent T-cell or antibody-mediated rejection and underlying chronic allograft nephropathy.