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Biomedical subjects

J D Scandling

Publications and source records attributed to J D Scandling.

At least 19 recordsLinked to original sources
PubMed2000

Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation.

Many complications after renal transplantation can be prevented if they are detected early. Guidelines have been developed for the prevention of diseases in the general population, but there are no comprehensive guidelines for the prevention of diseases and complications after renal transplantation. Therefore, the Clinical Practice Guidelines Committee of the American Society of Transplantation developed these guidelines to help physicians and other health care workers provide optimal care for renal transplant recipients. The guidelines are also intended to indirectly help patients receive the access to care that they need to ensure long-term allograft survival, by attempting to systematically define what that care encompasses. The guidelines are applicable to all adult and pediatric renal transplant recipients, and they cover the outpatient screening for and prevention of diseases and complications that commonly occur after renal transplantation. They do not cover the diagnosis and treatment of diseases and complications after they become manifest, and they do not cover the pretransplant evaluation of renal transplant candidates. The guidelines are comprehensive, but they do not pretend to cover every aspect of care. As much as possible, the guidelines are evidence-based, and each recommendation has been given a subjective grade to indicate the strength of evidence that supports the recommendation. It is hoped that these guidelines will provide a framework for additional discussion and research that will improve the care of renal transplant recipients.

Ambulatory Care↗
PubMed1999

Power Doppler imaging of acute renal transplant rejection.

PURPOSE: We evaluated the usefulness of power Doppler imaging (PDI) in diagnosing acute renal-transplant rejection. METHODS: Twenty-eight patients underwent 33 renal-transplant biopsies for suspected acute rejection. Patterns of renal parenchymal vascularity revealed by PDI in patients with abnormal biopsy results were compared with patterns in a group who had normal biopsy results. PDI examinations were reviewed retrospectively by 2 independent radiologists who had no knowledge of the biopsy results. A PDI diagnosis of acute rejection required marked vascular pruning in both the cortex and medulla. PDI results then were compared with transplant-biopsy results. RESULTS: The sensitivity and specificity of PDI for diagnosing acute renal-transplant rejection were 40% and 100%, respectively. None of the patients with negative biopsy results had PDI abnormalities. The negative predictive value of PDI was 33%, and the positive predictive value was 100%. CONCLUSIONS: In our study, an abnormal sonogram was highly predictive of acute transplant rejection. However, a normal sonogram did not exclude the possibility of rejection.

Acute Disease↗
PubMed1999

Dual kidney transplantation: older donors for older recipients.

BACKGROUND: Dual kidney transplantation, the transplantation of both donor kidneys into a single recipient, allows increased use of expanded criteria donors (eg, older donors with a history of hypertension) to alleviate the disparity between available donors and potential recipients. We evaluated outcomes in our dual kidney transplant program that started in 1995. STUDY DESIGN: A retrospective comparison of donor and recipient data between recipients of dual (n = 41) versus single (n = 199) cadaveric renal transplants from February 1, 1995, to March 22, 1998, was performed. Dual kidney transplantation was selectively performed when the calculated donor admission creatinine clearance was less than 90 mL/min and the donor age was greater than 60 years, or if the donor had an elevated terminal serum creatinine. Every attempt was made to age- and size-match the donor and recipients. RESULTS: Recipients of dual kidneys had donors who were older than single kidney donors (59 +/- 12 versus 42 +/- 17 years respectively, p < 0.0001) and had more hypertension (51% versus 29%, p = 0.024). Average urine output was lower in the dual versus single kidney group (252 +/- 157 versus 191 +/- 70 mL/hr, p = 0.036). Donors for dual kidney recipients had a lower donor admission creatinine clearance of 82 +/- 28 mL/min versus 105 +/- 45 mL/min in the single kidney group (p = 0.005). Recipients of dual versus single kidneys were older (58 +/- 11 versus 47 +/- 12 years, p > 0.0001). Dual versus single kidney recipients had similar serum creatinines up to 2 years posttransplant (1.6 +/- 0.3 versus 1.6 +/- 0.7 mg/dL at 2 years, p = NS) and a comparable incidence of delayed graft function (24% versus 33%, p = NS) and 3-month posttransplant creatinine clearance (54 +/- 23 versus 57 +/- 25 mL/min, p = NS). One-year patient and graft survival for single kidney transplantation was 97% and 90%, respectively, and 98% and 89% for dual kidney transplantation (p = NS). CONCLUSIONS: Dual kidney donors were significantly older, had more hypertension, lower urine outputs, and lower donor admission creatinine clearance. Despite these differences, dual kidney recipients had comparable postoperative function, outcomes, and survival versus single kidney recipients. We believe selective use of dual kidney transplantation can provide excellent outcomes to recipients of kidneys from older donors with reduced renal function.

Adult↗
PubMed1999

Sodium reabsorption and distribution of Na+/K+-ATPase during postischemic injury to the renal allograft.

BACKGROUND: A loss of proximal tubule cell polarity is thought to activate tubuloglomerular feedback, thereby contributing to glomerular filtration rate depression in postischemic acute renal failure (ARF). METHODS: We used immunomicroscopy to evaluate the segmental distribution of Na+/K+-ATPase in tubules of recipients of cadaveric renal allografts. Fractional excretion (FE) of sodium and lithium was determined simultaneously. Observations were made on two occasions: one to three hours after graft reperfusion (day 0) and again on post-transplant day 7. An inulin clearance below or above 25 ml/min on day 7 was used to divide subjects into groups with sustained (N = 15) or recovering (N = 16) ARF, respectively. RESULTS: In sustained ARF, the fractional excretion of sodium (FENa) was 40 +/- 6% and 11 +/- 5%, and the fractional excretion of lithium (FELi) was 76 +/- 5% and 70 +/- 2% on days 0 and 7, respectively. Corresponding findings in recovering ARF were 28 +/- 2% and 6 +/- 2% for the FENa and 77 +/- 4% and 55 +/- 3% (P < 0.05 vs. sustained) for FELi. Na+/K+-ATPase distribution in both groups was mainly basolateral in distal straight and convoluted tubule segments and collecting ducts. However, Na+/K+-ATPase was poorly retained in the basolateral membrane of proximal convoluted and straight tubule segments in sustained and recovering ARF on both days 0 and 7. CONCLUSIONS: We conclude that loss of proximal tubule cell polarity for Na+/K+-ATPase distribution is associated with enhanced delivery of filtered Na+ to the macula densa for seven days after allograft reperfusion. Whether an ensuing activation of tubuloglomerular feedback is an important cause of glomerular filtration rate depression in this form of ARF remains to be determined.

Acute Kidney Injury↗
PubMed1999

PAH extraction and estimation of plasma flow in human postischemic acute renal failure.

We determined the effect of postischemic injury to the human renal allograft on p-aminohippurate (PAH) extraction (E(PAH)) and renal blood flow. We evaluated renal function in 44 allograft recipients on two occasions: 1-3 h after reperfusion (day 0) and again on postoperative day 7. On day 0 subsets underwent intraoperative determination of renal blood flow (n = 35) by Doppler flow meter and E(PAH) (n = 25) by renal venous assay. Blood flow was also determined in another subset of 16 recipients on postoperative day 7 by phase contrast-cine-magnetic resonance imaging, and E(PAH) was computed from the simultaneous PAH clearance. Glomerular filtration rate (GFR) on day 7 was used to divide subjects into recovering (n = 23) and sustained (n = 21) acute renal failure (ARF) groups, respectively. Despite profound depression of GFR in the sustained ARF group, renal plasma flow was only slightly depressed, averaging 296 +/- 162 ml. min(-1). 1.73 m(-2) on day 0 and 202 +/- 72 ml. min(-1). 1.73 m(-2) on day 7, respectively. These values did not differ from corresponding values in the recovering ARF group: 252 +/- 133 and 280 +/- 109 ml. min(-1). 1.73 m(-2), respectively. E(PAH) was profoundly depressed on day 0, averaging 18 +/- 14 and 10 +/- 7% in recovering and sustained ARF groups, respectively, vs. 86 +/- 6% in normal controls (P < 0.001). Corresponding values on day 7 remained significantly depressed at 65 +/- 20 and 11 +/- 22%, respectively. We conclude that postischemic injury to the renal allograft results in profound impairment of E(PAH) that persists for at least 7 days, even after the onset of recovery. An ensuing reduction in urinary PAH clearance results in a gross underestimate of renal plasma flow, which is close to the normal range in the initiation, maintenance, and recovery stages of this injury.

Acute Kidney Injury↗
PubMed1998

Backleak, tight junctions, and cell- cell adhesion in postischemic injury to the renal allograft.

Postischemic injury in recipients of 3-7-d-old renal allografts was classified into sustained (n = 19) or recovering (n = 20) acute renal failure (ARF) according to the prevailing inulin clearance. Recipients of optimally functioning, long-standing allografts and living donors undergoing nephrectomy served as functional (n = 14) and structural controls (n = 10), respectively. Marked elevation above control of fractional clearance of dextrans of graded size was consistent with transtubular backleak of 57% of filtrate (inulin) in sustained ARF. No backleak was detected in recovering ARF. To explore a structural basis for backleak, allograft biopsies were taken intraoperatively, 1 h after reperfusion in all recipients, and again on day 7 after transplant in a subset (n = 10). Electron microscopy revealed disruption of both apical and basolateral membranes of proximal tubule cells in both sustained and recovering ARF, but cell exfoliation and tubule basement membrane denudation were negligible. Histochemical analysis of membrane-associated adhesion complexes confirmed an abnormality of proximal but not distal tubule cells, marked in sustained ARF but not in recovering ARF. Staining for the zonula occludens complex (ZO-1) and adherens complex (alpha, beta, and gamma catenins) revealed diminished intensity and redistribution of each cytoskeletal protein from the apico-lateral membrane boundary. We conclude that impaired integrity of tight junctions and cell-cell adhesion in the proximal tubule provides a paracellular pathway through which filtrate leaks back in sustained allograft ARF.

Acute Kidney Injury↗
PubMed1998

A review of the kidneys that nobody wanted: determinants of optimal outcome.

BACKGROUND: We previously reported excellent outcome at 6 months after transplantation in recipients of expanded criteria donor kidneys that other local centers had declined, kidneys that nobody wanted (KNW), versus controls. We now report follow-up after 23 months. METHODS: We retrospectively reviewed 27 donor and 24 recipient characteristics in 126 adult recipients of transplants from January 1, 1995, to November 25, 1996. RESULTS: Donors of control kidneys versus KNW were younger and had significantly higher minimum 4-hr urine output. Recipients of control kidneys versus KNW had significantly more HLA matches and lower 3-month posttransplant serum creatinine levels. Patient and graft survival rates were similar between the control kidneys versus the KNW. We also compared the control kidneys and KNW with regard to prompt function or delayed graft function and satisfactory versus unsatisfactory function (unsatisfactory: serum creatinine > or =2.5 ml/dl or graft loss at 6 months) to identify donor and recipient characteristics associated with delayed graft function and unsatisfactory outcome. The incidence of rejection was significantly lower in control kidneys and KNW with satisfactory function versus control kidneys and KNW with unsatisfactory function. CONCLUSIONS: These data demonstrate: (1) similar graft survival at 12 months, (2) lower donor age, (3) higher minimum 4-hr urine output, and (4) more HLA matches in recipients of control kidneys versus KNW. Optimal outcome was achieved in recipients of control kidneys and KNW with prompt function and satisfactory function based upon serum creatinine in the first 6 months and in recipients with lower rates of rejection. Although outcome is dependent upon many donor and recipient variables, we believe that with careful donor and recipient selection, excellent outcome can be achieved using expanded criteria donor kidneys.

Actuarial Analysis↗
PubMed1998

Outcome in cadaveric renal transplant recipients treated with cyclosporine A and mycophenolate mofetil versus cyclosporine A and azathioprine.

BACKGROUND: Recent multicenter reports have demonstrated improved outcome in recipients of cadaveric renal transplants treated with mycophenolate mofetil (MMF) versus azathioprine (AZA) in combination with cyclosporine A (CSA) and prednisone. We compared the outcome at our center in patients treated with MMF versus AZA, CSA, and prednisone. METHODS: We retrospectively reviewed 242 adult cadaveric renal transplant recipients treated between 11/91 and 5/97. We compared 25 donor variables and 27 recipient variables and outcome parameters between patients treated with MMF versus AZA. There were 117 patients treated with CSA+AZA, 84 with CSA+MMF, and 42 who received other immunosuppressive strategies. RESULTS: There were no significant differences in any clinically important donor variables. Patients treated with MMF versus AZA and CSA had significantly fewer rejections and readmissions. There was no significant difference in 1- or 2-year patient survival. Recipients treated with MMF had a 5% higher graft survival at 2 years, although the difference did not reach statistical significance. CONCLUSIONS: Outcome is improved in adult recipients of cadaveric renal transplants treated with MMF versus AZA in combination with CSA and prednisone.

Adult↗
PubMed1998

Plasma glutathione peroxidase and its relationship to renal proximal tubule function.

Selenium-dependent extracellular glutathione peroxidase (E-GPx) is found in plasma and other extracellular fluids. Previous studies have indicated that patients with chronic renal failure on dialysis have low plasma GPx activity. In this study, dialysis patients had approximately 40% of control plasma GPx activity, while anephric individuals had lowest plasma GPx activities ranging from 2 to 22% of control. The residual plasma GPx activity in anephric individuals could be completely precipitated by anti-E-GPx antibodies, indicating that all plasma GPx activity can be attributed to E-GPx in both normal and anephric individuals. Plasma GPx activity rises rapidly following kidney transplantation, often reaching normal values within 10 days. The plasma GPx activity in some transplanted patients rises to levels higher than the normal range, followed by a return to the normal range. Since E-GPx in the kidney is primarily synthesized in the proximal tubules, we investigated whether nephrotoxic agents known to disrupt proximal tubule function also affected plasma GPx activity. The beta-lactam antibiotic cephaloglycin rapidly caused a decrease in plasma GPx activity in rabbits. In addition, the chemotherapeutic agent ifosfamide caused a decrease in plasma GPx activity in pediatric osteosarcoma patients. Fanconi syndrome associated with either ifosfamide therapy or valproic acid therapy also caused a decrease in plasma GPx activity. Thus plasma GPx activity is related to kidney function and is decreased in certain situations where nephrotoxic drugs are administered. Monitoring plasma GPx activity may have predictive value in evaluating the function of transplanted kidneys or in predicting those patients particularly at risk of nephrotoxic injury associated with certain medications.

Adult↗
PubMed1998

What is the optimal approach for the end-stage diabetic nephropathy patient considering simultaneous pancreas-kidney transplantation?

This case-based discussion regards two very different patients with end-stage diabetic nephropathy (ESDN) who are considering transplantation. What is the best approach for each individual: pancreas-kidney transplant or kidney transplant alone? Suppose a live kidney donor is available? What are the risks and benefits of each approach? In the candidate evaluation process, medical issues, such as uncorrectable coronary artery disease, are investigated and may preclude transplantation altogether or dictate the optimal approach. Similarly, a careful psychosocial profile is important to tailor the approach to the patient. The multidisciplinary transplant team has an obligation to provide informed consent, foster realistic expectations, and advise the candidate based on collective expertise. Ultimately, the decision as to the best course-pancreas-kidney, kidney transplant alone, or no transplantation-is the result of a collaborative effort between the patient and the transplant team.

Adult↗
PubMed1997

Outcomes in diabetic patients after simultaneous pancreas-kidney versus kidney alone transplantation.

BACKGROUND: Previous studies have identified more morbidity in simultaneous pancreas-kidney (SPK) transplant recipients compared with kidney alone (KA) recipients. With the development of novel immunosuppressive drugs, studies are needed to determine optimal treatment regimens in specific patient populations. METHODS: We retrospectively compared short-term outcome in diabetic patients receiving either SPK or KA transplantation from December 10, 1991, to July 31, 1996. The SPK recipients received either cyclosporine (CsA) + azathioprine (AZA), FK506+AZA, or FK506 + mycophenolate mofetil (MM). KA group patients received either CsA+AZA or CsA+MM. RESULTS: Recipients of SPK instead of KA transplants were younger, had a longer mean length of stay, had a decreased incidence of delayed graft function, and had more readmissions. There were no significant differences in serum creatinine at 1, 2, and 3 years after transplantation, number of rejection episodes and infections, incidence of kidney graft loss and patient death, and 1- and 3-year actuarial patient and kidney graft survival rates between the two groups. Diabetic SPK patients receiving FK506+MM had a higher mean 3-month creatinine clearance (calculated), compared with recipients of CsA+AZA or FK506+AZA. Diabetic patients after KA transplantation who received CsA+MM demonstrated fewer rejection episodes and graft losses, although differences did not reach statistical significance. CONCLUSIONS: (1) Diabetic SPK recipients have decreased rates of delayed graft function and more readmissions compared with diabetic KA recipients. (2) There is no difference in: serum creatinine levels up to 3 years after transplantation, number of rejection episodes or infections, and 1- and 3-year patient and graft survival rates between SPK and KA recipients. (3) Short-term outcome is improved in diabetic recipients of SPK and KA transplants receiving MM instead of AZA.

Adolescent↗
PubMed1997

When should expanded criteria donor kidneys be used for single versus dual kidney transplants?

BACKGROUND: To increase the utilization of cadaveric donor kidneys, we have recently expanded our acceptable criteria to include aged donors (frequently with a history of hypertension), by selectively using both donor kidneys (dual transplant) into a single recipient. METHODS: To define when these expanded criteria donor (ECD) kidneys should be used as a single versus a dual kidney transplant, we retrospectively reviewed 52 recipients of ECD kidneys that had been turned down by all other local centers between 1/1/95 and 11/15/96. Fifteen patients received dual transplants, whereas the remaining 37 received single kidneys. Of the dual kidney recipients, 14 of 15 ECD were > or = 59 years of age, 10 of 15 were hypertensive, and 9 of 15 were both. Of the single recipients, 11 of 37 ECD were > or = 59 years of age, 11 of 37 were hypertensive, and 7 of 37 were both. All patients received cyclosporine-based triple-drug therapy. We compared seven donor (D) and sixteen recipient outcome variables in single versus dual kidney transplants as subgrouped by: (1) donor admission creatinine clearance (D-AdC(Cr)) < 90 ml/min; (2) D-age > or = 59 years; and (3) cold storage (Cld Stg) < or > 24 hr. RESULTS: In the group with D-AdC(Cr) < 90, there was a significantly higher incidence of delayed graft function (DGF) in single versus dual recipients (9 of 20 [45%] vs. 1 of 11 [9%]; P=0.04) and worse early graft function based upon mean serum creatinine at 1 and 4 weeks (5.3+/-3.3 and 2.8+/-2.0 vs. 1.7+/-0.6 and 1.4+/-0.5 mg] dl; P<0.05). In the group with D-age > or = 59, recipients of single kidneys had significantly higher mean serum creatinine at 1, 4, and 12 weeks versus recipients of dual kidneys (5.1+/-3.3, 3.4+/-2.1, 2.8+/-1.5 versus 2.8+/-2.5, 1.5+/-0.6, 1.6+/-0.5 mg/dl; P<0.05). Cld Stg time also had an impact on DGF and early outcome. Recipients of dual kidneys stored less than 24 hr had a significantly lower incidence of DGF versus single kidneys stored more than 24 hr (10% vs. 46%; P<0.05) and better early graft function based on mean serum creatinine at 1, 4, and 12 weeks (1.9+/-0.8, 1.3+/-0.4, 1.5+/-0.2 vs. 6.6+/-3.4, 3.0+/-1.6, 2.9+/-1.9 mg/dl; P<0.05). The overall 1-year patient and graft survivals were 96% and 81% vs. 93% and 87% (P=NS) in recipients of single ECD versus dual ECD kidneys. CONCLUSIONS: In conclusion, we believe that kidneys from ECD with D-AdC(Cr) < 90 ml/min and D-age > or = 59 should be used as dual kidney transplants, keeping the Cld Stg time at < 24 hr to minimize the effect of Cld Stg on early graft function.

Adult↗
PubMed1997

Eradication of cytomegalovirus reactivation disease using high-dose acyclovir and targeted intravenous ganciclovir in kidney and kidney/pancreas transplantation.

BACKGROUND: The attack rate of cytomegalovirus (CMV) is over 50% in solid organ transplant recipients at risk for primary CMV infection and in those receiving antilymphocyte antibody therapy. Various CMV prophylaxis regimens over the last few years have reduced the attack rate to around 20% overall. METHODS: We report our results using high-dose acyclovir for 3 months after transplant, with targeted intravenous ganciclovir for the duration of any antilymphocyte antibody therapy, in our kidney and simultaneous pancreas/kidney transplant recipients. Records of 109 consecutive patients over a 2-year period were reviewed. RESULTS: Six cases of CMV disease were identified. Five cases occurred in 21 patients at risk for primary CMV disease (24%), whereas only one case occurred in 73 patients at risk for CMV reactivation (1.4%). CONCLUSION: We conclude that high-dose acyclovir and targeted ganciclovir is excellent prophylaxis against CMV reactivation in kidney and simultaneous pancreas/kidney transplantation.

Acyclovir↗
PubMed1997

Bladder augmentation can be problematic with renal failure and transplantation.

Ten consecutive patients with failure of urinary bladder augmentation (UBA) performed either prior to or after reaching end-stage renal disease (ESRD) were studied. Seven patients developed increased hydroureteronephrosis, infectious complications, and advanced to ESRD after UBA. The mean time to development of ESRD in patients who had UBA performed with moderate chronic renal failure (CRF) was 1.8 years. The UBAs in all seven patients were taken down prior to transplantation. Subsequently, five of these UBA-takedown patients have received kidney grafts and all have stable, good renal function. Three patients had their UBA performed after they reached ESRD, in preparation for renal transplantation. All three of these patients experienced recurrent urosepsis following transplantation, resulting in death in one patient and loss of graft in another. The third patient will undergo takedown of the UBA. This study suggests that UBA may possibly not be the best option for patients with moderate CRF and those awaiting transplantation.

Adolescent↗
PubMed1997

Pathophysiology of reduced glomerular filtration rate in delayed graft function.

Delayed graft function is a form of postischemic acute renal failure. It lowers glomerular filtration rate in large part by depressing the glomerular transcapillary hydraulic pressure difference, the driving force for the formation of filtrate. Loss of proximal tubule cell polarity, impaired sodium reabsorption and tubuloglomerular feedback-mediated afferent arteriolar constriction are all implicated. A link between delayed graft function and chronic allograft injury is evident. The ensuing impairment of graft survival makes urgent the need for further elucidation of delayed graft function and a search for an effective therapy.

Acute Kidney Injury↗
PubMed1997

Kidney and kidney/pancreas transplantation at Stanford University Medical Center.

The disparity between the supply of cadaveric donors and the demand for renal allografts continues to grow. We have taken a multifaceted approach to increase the allograft pool: 1. Spiral computed tomography to evaluate potential living kidney donors is safer, less invasive, less expensive and more time efficient and thus should encourage living organ donation. 2. Use of selected expanded criteria cadaveric donor kidneys (aged 60 or over, hypertensive) in size- and age-matched recipients have short-term function at 3 and 6 months comparable to standard cadaveric renal allografts. 3. Kidneys from expanded criteria donors over age 59 and with an adjusted creatinine clearance less than 90 ml/min should be used as a dual kidney transplant into an appropriate sized- and aged-matched recipient. 4. Kidneys from pediatric donors < 5 years of age should be utilized as en-bloc grafts, when transplanted into adult recipients. Pediatric renal transplantation poses numerous challenges given the different and problematic etiologies of ESRD, the surgical considerations in small children and infants and the enhanced immune response witnessed in children. Nevertheless, renal transplantation is clearly the therapy of choice for children with ESRD and excellent results can be obtained through strict adherence to surgical detail, tight immunosuppressive management, and aggressive fluid management in infants and small children. We feel it is also critically important that transplantation and follow-up care be carried out by an integrated and experienced surgical and medical team. Managed healthcare has had profound effects on the practice and management of transplantation centers. The one area of greatest impact has been the pressure upon programs to reduce their cost of transplantation. We have initiated a number of new outpatient treatment protocols as part of an effort to contain costs. Most patients with acute rejection are evaluated (including transplant kidney biopsy) and treated in an ambulatory setting. Completion of OKT3 therapy in selected patients is also performed at home through visiting nurses or at our ambulatory care center. Additionally, treatment of CMV disease is now performed almost exclusively on an outpatient basis.

Actuarial Analysis↗