Medical evaluation of living kidney donors with nephrolithiasis: a survey of practices in the United States.

BACKGROUND: A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. METHODS: We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. RESULTS: 49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. CONCLUSIONS: Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.

When the living and the deceased cannot agree on organ donation: a survey of US organ procurement organizations (OPOs).

The legal concept of first person authorization (FPA) is based on the principle that a decision by a person with decision-making capacity should be respected even after he or she dies. Although the transplant community largely supports this concept, its implementation has not been universal. We conducted a web-based survey of all 58 Organ Procurement Organization (OPO)executive directors in the United States to assess OPOs' procurement policies and practices in the context of family objections. All 58 respondents(100%) responded to our survey. All OPOs except one have an online donor registration website. Most OPOs(89%) (51 of 57 respondents) estimated that the frequency of family objecting to organ donation in cases of registered donors was <10%. No OPOs reported the frequency to be higher than 25%. Only 50% (27 of 54) of the OPOs have a written policy on handling family objections. Approximately 80% of the OPOs reported honoring FPA. However, in the past 5 years, 20 OPOs (35%) have not yet participated in organ procurement from a registered deceased donor over family objection. Further research to identify the barriers and possible solutions to implementing FPA is warranted.

KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.

Polyomavirus-associated nephropathy: update on antiviral strategies.

Polyomavirus-associated nephropathy (PVAN) is a major complication of kidney transplantation. Many centers respond to PVAN by reducing immunosuppression. Concern over precipitating rejection, as well as situations in which some PVAN-afflicted individuals have multi-organ transplants, can make reduction of immunosuppression undesirable. In these cases, effective antiviral strategies would be useful. This article describes clinical observations and experiences with 3 different antiviral protocols. Two protocols address antiviral treatment of nephropathy (cidofovir in one, and leflunomide in the other). The third protocol examines fluoroquinolone control of polyoma urinary excretion. Patients responded to all 3 strategies. These promising approaches deserve further evaluation with prospective controlled studies.

Granulomatous tubulointerstitial nephritis in the renal allograft.

Granulomatous tubulointerstitial nephritis has rarely been described in renal allografts. Of 1,574 renal allograft tissue specimens obtained from 514 patients in the period 1993 to 1998, we report three cases (0.6%) with interstitial nephritis containing multiple noncaseating granulomas. Biopsy specimen 1 was obtained from a 44-year-old woman with a 6-day history of systemic Candida albicans infection and showed multiple granulomas containing budding yeasts. Biopsy specimen 2 was from a 33-year-old man who presented with miliary spread of Mycobacterium tuberculosis 12 days before the allograft biopsy. Biopsy specimen 3 was from a 23-year-old woman who presented with Escherichia coli urinary infection and bacteremia that was treated with antibiotics for 10 days before the biopsy. Granulomatous inflammation in reponse to infectious agents or drugs in immunosuppressed kidney transplant recipients can rarely give rise to allograft interstitial nephritis that is distinct from acute rejection. To our knowledge, there are no prior reports of granulomatous tubulointerstitial nephritis associated with C albicans and E coli infection or antibiotic therapy in human renal allografts.

Drug-induced acute interstitial nephritis in renal allografts: histopathologic features and clinical course in six patients.

Drug-induced acute interstitial nephritis is a common cause of dysfunction in native kidneys, but is rarely reported in renal allografts. This report describes six renal transplant recipients with acute renal allograft dysfunction or delayed allograft function in whom a renal transplant biopsy showed histopathologic features of drug-induced interstitial nephritis with no diagnostic evidence of acute rejection, cyclosporine or tacrolimus nephrotoxicity, or other lesion that could account for the graft dysfunction. In five of the six patients, interstitial nephritis occurred within 4 weeks of transplantation. All the patients were receiving trimethaprim-sulfamethoxazole and/or other drugs associated with interstitial nephritis. After discontinuation of these drugs and short-term corticosteroid treatment, all patients showed improvement in renal function, although the time course of this improvement varied considerably, with three patients showing a return to baseline serum creatinine level within 2 weeks and two patients showing a gradual improvement over 8 weeks. Four of the five patients followed up for more than 1 year (range, 14 to 33 months) after the episode of interstitial nephritis had good allograft function (serum creatinine level

Smooth muscle-specific actin levels in the urine of renal transplant recipients: correlation with cyclosporine or tacrolimus nephrotoxicity.

Cyclosporine A (CSA) and tacrolimus (FK506) are powerful immunosuppressive agents that have proven useful for antirejection therapy in patients with solid organ transplants, including kidney. However, both drugs are nephrotoxic, each producing similar histological patterns of injury to renal tubules and preglomerular arterioles, and this toxicity is a major cause of renal allograft dysfunction. A renal transplant biopsy presently represents the most reliable means of diagnosing nephrotoxicity caused by CSA or tacrolimus and distinguishing it from acute rejection. Because CSA and tacrolimus nephrotoxicity often involve arteriolar smooth muscle, whereas vascular smooth muscle is rarely involved in acute rejection, we investigated if the appearance of a smooth muscle-specific isoform of alpha-actin (SMA) in the urine of renal transplant recipients about to undergo a biopsy for graft dysfunction correlated with biopsy evidence of CSA or tacrolimus toxicity. Eighty-nine urine samples from 61 patients, plus 6 samples from healthy control subjects, were analyzed in a blinded manner by enzyme-linked immunosorbent assay using a specific anti-SMA monoclonal antibody. For the patient samples, the results of these assays were then correlated with the biopsy findings. Those 40 cases in which the biopsy showed evidence of CSA or tacrolimus nephrotoxicity had a significantly (P < 0.01) greater SMA level in the corresponding urine samples (0.089 +/- 0.126 microgram/mL; mean +/- SD) than the 49 cases without toxicity (0.018 +/- 0.027 microgram/mL) or 6 control subjects (0.003 +/- 0.007 microgram/mL), although there was considerable overlap of SMA values among these groups. The greatest SMA levels were seen in patients with CSA or tacrolimus nephrotoxicity that was likely to be relatively acute, namely those with thrombotic microangiopathy and those without previous biopsy evidence of toxicity. SMA levels correlated significantly with the estimated severity of arteriolopathy on biopsy. In patients with tubular but not arteriolar lesions of CSA or tacrolimus toxicity, the mean SMA level was not significantly greater than that in patients without toxicity. Urine SMA levels in patients with a biopsy specimen showing acute rejection were not significantly different from those in patients without rejection, and there was no correlation between urine SMA level and severity of rejection. Whereas the degree of overlap of SMA levels in patients with and without nephrotoxicity was far too great to consider this assay as a potential alternative to renal transplant biopsy for the diagnosis of nephrotoxicity, the assay may have potential as a marker for active arteriolar injury in renal transplant recipients and other patients receiving CSA or tacrolimus therapy.

Pregnancy in a nonimmunosuppressed transplant recipient.

A 30-year-old woman with a living related six-antigen-matched kidney allograft conceived 10 years posttransplantation. She had discontinued her immunosuppression medications 3 years previously. The allograft functioned well throughout gestation, which was complicated by preeclampsia, leading to induction at 35 weeks and delivery of a 2,175-g male.

A retrospective study of kidney transplant recipients from living unrelated donors.

Due to the shortage of cadaveric organs, kidneys from living unrelated donors (LUD) are increasingly being used for transplantation. The long-term outcome for LUD recipients is not completely known. This study was undertaken to evaluate the long-term graft survival in LUD recipients and compare it with that of cadaver donor allograft recipients. Three hundred and sixty-four LUD and 3881 cadaveric kidney recipients were evaluated using data obtained through the Brazilian Renal Transplant Registry. Transplants performed between January 1, 1987, and June 30, 1996, were eligible for analysis. Graft and patient survival were estimated by the Kaplan-Meier method. Sixty percent of the LUD were from spouses. The median duration of follow-up was 23.8 mo (0 to 117.2 mo). Patient survival rates were not significantly different for LUD and cadaveric kidney recipients (69% [95% confidence interval (CI), 61.9 to 76.1%] versus 73.2% [71 to 75.4%] at 5 yr; 69% [61.9 to 76.1%] versus 60.6% [55.1 to 66.1%] at 9.6 yr). Graft survival rates for recipients of LUD allografts were similar to those for cadaveric kidneys at 5 yr (50.1% [43.2 to 57%] versus 50.4% [48.1 to 52.8%]) and higher, although not significantly, at 9.6 yr (45.7% [37.7 to 53.7%] versus 32.7% [26.4 to 39%], respectively, P = 0.14). In a multivariate analysis using the Cox proportional hazards regression model, after adjusting for recipient age, race, history of previous transplantation, and year of transplantation, the risk of graft failure was 16% (95% CI, -3% to 31%) lower for LUD than cadaveric recipients. We conclude that LUD are an excellent alternative to cadaveric kidney donors. The long-term patient and graft survival rates for recipients of LUD allografts are at least as good as those for recipients of cadaveric kidneys.

Analysis of fracture prevalence in kidney-pancreas allograft recipients.

Fractures occur in 11 to 26% of renal allograft recipients after transplantation despite improvements in bone and mineral disorders. This high fracture rate is likely a consequence of accelerated osteopenia. The cause of posttransplant bone loss is multifactorial, and patients with insulin-dependent diabetes mellitus and renal failure may have additional fracture risks such as low turnover bone disease. This retrospective cohort study was undertaken to determine the long-term incidence and the potential risk factors of posttransplant fractures in patients with insulin-dependent diabetes mellitus undergoing combined kidney-pancreas allograft transplantation. Thirty-five patients with insulin-dependent diabetes mellitus who received a combined kidney-pancreas allograft between 1987 and 1992 were evaluated. Thirty-five kidney allograft recipients matched for age, gender, and the date of transplant were also reviewed. The fracture incidence in the kidney-pancreas group was 49% after transplantation. The rate of first fracture after kidney-pancreas transplantation was 12.1% per patient year, resulting in a 5-yr fracture-free rate of 48%. The initial fracture occurred at a mean of 31.06 +/- 19.9 mo. Steroid exposure was found to increase the risk of fracture, and analysis by means of a Cox regression model estimated that an increase in cumulative steroid exposure of 10 mg/kg at any given month increased the hazard of sustaining a fracture by 9% (95% confidence interval for hazard ratio, 1.01 to 1.18; P = 0.031). This analysis suggests that kidney-pancreas recipients are at significant risk of sustaining a fracture within a few years after transplantation.

Performance measurement in pneumonia care: beyond report cards.

OBJECTIVE: To compare the medical management of bacteremic pneumococcal pneumonia at a university-based and a community-based teaching hospital and evaluate strategies for performance measurement and subsequent improvement. DESIGN: We conducted a retrospective cohort study involving a 450-bed university hospital in the inner city and a 400-bed private hospital in a rural community. MATERIAL AND METHODS: The medical records of all adults with bacteremic pneumococcal pneumonia admitted to a university and a community hospital during a 5-year period were reviewed. Information about patient age, sex, underlying medical condition, severity of disease, health-care insurance, management, and outcome was collected and analyzed. RESULTS: Patients at the two hospitals were similar in underlying illnesses and severity of disease. In comparison with the community hospital, resource expenditure was greater at the university hospital, where all 11 identified diagnostic measures and treatment resources were used more often. This difference was statistically significant for sputum cultures, all cultures, and lumbar punctures. Despite the greater intensity of care, in-hospital mortality was higher at the university hospital (26%) than at the community hospital (12%) (P>0.1). CONCLUSION: The outcome of bacteremic pneumococcal pneumonia did not differ significantly at a university hospital in comparison with a community teaching hospital, even though resource expenditure at the university hospital was greater. Our findings suggest that hospital "report cards" based solely on outcome comparisons provide inadequate information. In contrast, examination of variations in profiles of resource utilization can detect important differences in hospitals and can be used to guide continuous quality improvement efforts and ultimately improve hospital care.

Reversal of accelerated renal allograft rejection with FK 506.

Although FK 506 has been shown to effectively reverse refractory renal allograft rejection, its ability to reverse accelerated renal allograft rejection as a primary agent has not been specifically addressed. Herein evidence of the ability of FK 506 to reverse accelerated renal allograft rejection is presented. A 16-yr-old highly sensitized (PRA 75%) male underwent a second cadaveric renal transplant procedure. Despite induction immunosuppression with ATGAM, cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum creatinine (1.6-->2.1 ng/dl) and reduction in urine output (4000 ml/d-->1000 ml/d) were observed on the sixth post-transplant day. Renal allograft biopsy performed at that time revealed typical features of accelerated rejection including neutrophil margination in glomerular and interstitial capillaries, and C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by immunofluorescence). FK 506 therapy was promptly instituted and ATGAM therapy discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/dl) and subsequently progressively dropped to 1.2 mg/dl. Repeat biopsy on FK 506 treatment day 12 revealed marked histologic improvement. Renal function remains excellent (1.3 mg/dl) 18 months after initiation of FK 506 therapy, and recurrent rejection has not been observed. This experience provides evidence that FK 506 therapy may effectively reverse accelerated renal allograft rejection, and that it provides a means for treating antibody-mediated mechanisms of allograft rejection.

Tacrolimus therapy for refractory acute renal allograft rejection: definition of the histologic response by protocol biopsies.

UNLABELLED: Protocol biopsies were performed to define the histologic response to tacrolimus therapy in patients with refractory acute renal allograft rejection. Renal allograft biopsies were performed at defined intervals after initiation of tacrolimus therapy. Protocol biopsies were performed before tacrolimus therapy (within 48 hr of initiation of therapy) and after 1 week of therapy. If the 1-week biopsy did not show rejection reversal, repeat protocol biopsies were obtained at 1- to 2-week intervals, until histologic reversal was observed. Additional biopsies were obtained at 4 weeks and at 8-12 weeks after initiation of tacrolimus therapy. Indicated biopsies were also performed to evaluate increases in serum creatinine. A total of 92 biopsies were performed in 23 patients (average 4.0 biopsies/ patient). Biopsies were performed in each patient immediately before starting tacrolimus therapy (23 biopsies), and 69 biopsies (3.0 biopsies/patient) were performed during tacrolimus therapy. Rejection diagnosis was based on strict Banff criteria. Pretacrolimus biopsies demonstrated mild acute rejection in 64% of patients and moderate acute rejection in 36%. One week after initiation of tacrolimus therapy, protocol biopsies revealed the following: no rejection (60%), improvement (13%), no change (20%), and worsening rejection (7%). Histologic changes at 1 week did not correlate with changes in renal function, as 63% of patients that showed histologic improvement or reversal during the first 2 weeks of therapy did not show improvement in serum creatinine. A lack of histologic improvement (or worsening) at 1 week was demonstrated in a significant proportion of patients (27%); increased tacrolimus dosing provided rejection reversal or improvement in 1-2 weeks in each of these patients. Recurrent rejection was diagnosed on eight biopsies in seven patients, however six episodes were diagnosed by protocol biopsies alone (i.e., in the absence of an elevation in serum creatinine). Delayed improvement in renal function, despite histologic reversal, was likely due to physiologic effects of tacrolimus (i.e., afferent arteriolar vasoconstriction), as histologic evidence of tacrolimus toxicity was not observed during the first 2 weeks of therapy. Histologic evidence of tacrolimus nephrotoxicity (nodular arteriolar hyalinosis) was found in 21% (15 of 69) of biopsies in 39% of patients (9 of 23) at a median time of 60 days (range 12-150 days). Tacrolimus dose and blood levels (by IMx assay) did not correlate with development of clinically silent or clinically evident nephrotoxicity. IN CONCLUSION: 1) protocol biopsies provide information that allows individualization of tacrolimus rejection therapy, 2) histologic resolution of rejection often precedes biochemical improvement, 3) histologic evidence of tacrolimus nephrotoxicity is seldom observed in the first 2 weeks of therapy, and 4) clinically silent recurrent rejection and clinically silent tacrolimus nephrotoxicity are observed with significant frequency during tacrolimus therapy for refractory renal allograft rejection.

Long-term outcome of kidney-pancreas transplant recipients with good graft function at one year.

To assess the long-term outcome of kidney/pancreas transplantation, patients were identified who had good graft function at one year posttransplant and a minimum of 3 years' follow-up. Fifty recipients from 1987-92 met these criteria. Records were reviewed for graft survival, graft function, readmissions, and medical complications. Psychosocial adjustment and quality of life were assessed using the SCL-90-R and SIP surveys, respectively. Patient, kidney, and pancreas survivals were 94%, 86%, and 85% at five years (Kaplan-Meier), with a mean follow-up of 4.3 years. The 3 deaths were due to 2 sudden arrests at home (presumed to be cardiac events) and 1 episode of sepsis. Other graft losses were due to rejection, except for one case of sepsis. The remaining patients are normoglycemic (glucose 92 +/- 23 mg/dl) and have a creatinine of 1.8 +/- 0.6 mg/dl. Mortality after the first year was 0.9%/year. Estimated kidney and pancreas half-lives were 15 +/- 2 and 23 +/- 7 years, respectively. Hospitalization, acute rejection, graft pancreatitis, dehydration, and severe infections all decreased dramatically after the first year. While CMV was the most common infection in the first year, foot infections predominated thereafter. Retinal hemorrhage was infrequent. Sudden death (presumably cardiac) was the chief cause of mortality, while peripheral vascular disease resulted in several amputations. Fractures were common, suggesting the need for increased attention to bone demineralization. Psychosocial and quality of life evaluations were within normal limits. In conclusion, most complications specifically related to transplantation occur in the first year, but underlying disease renders these patients susceptible to a variety of cardiovascular, bone, and other disorders.