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Biomedical subjects

W E Braun

Publications and source records attributed to W E Braun.

At least 19 recordsLinked to original sources
PubMed2006

Assessing glomerular filtration rate by estimation equations in kidney transplant recipients.

Surveillance of glomerular filtration rate (GFR) is crucial in the management of kidney transplant recipients. With special emphasis on serum creatinine (SCr) calibration assay, we assessed the performance of estimation equations as compared to iothalamate GFR (iGFR) in 209 patients using the modification of diet in renal disease (MDRD), Nankivell and Cockcroft-Gault methods. Fifty-five percent of patients were treated with a calcineurin inhibitor (CNI) and all were taken trimethroprim-sulfametoxazole at the time of SCr measurement. The mean iGFR was 44 +/- 26 mL/min/1.73 m2. The MDRD equation showed a median difference of 0.9 mL/min/1.73 m2 with 53% of estimated GFR within 20% of iGFR. Median differences were 7.5 and 7.0 mL/min/1.73 m2 for Nankivell and Cockcroft-Gault formulas, respectively. The accuracy of the Nankivell and Cockcroft-Gault formulas was such that only 38% and 37% of estimations, respectively, fell within 20% of iGFR. The performance of all equations was not uniform throughout the whole range of GFR, with some deterioration at the extremes of GFR levels. In addition, good performance of the MDRD equation was seen in subjects taking CNI. In conclusion, the overall performance of the MDRD equation was superior to the Nankivell and Cockcroft-Gault formulas in renal transplant recipients including subjects treated with CNI.

Adult↗
PubMed2003

Long-term renal transplantation. Recent successes and new problems.

There has been continued improvement in preventing early biopsy-proved acute rejections and increasing 1-year allograft success rates, and, after some delay, the conditional half-life of grafts. Beneath these impressive achievements are several troubling concerns: unrecognized subclinical rejections; the emergence of acute and chronic humoral rejection; the different effect of certain acute rejections on the development of chronic rejection; the possibility that the current improvements in reducing early acute rejection may not be translated into longer half-life for the graft unless important adjunctive therapy is included. The use of cyclosporine (CSA) has been reshaped by lower dosing, conversion and avoidance protocols, C2 blood level monitoring, availability of generics, and application to non-transplant immunologically-mediated renal diseases. The enigma of chronic allograft nephropathy (CAN) unfortunately still remains, but recent studies on the effects of hypomagnesemia are provocative. The actual cohort of truly long-term renal transplant successes is providing remarkable insights into the way such grafts and their recipients achieve 30-year success. More than half of these patients have experienced early acute rejections (even Banff II and III). Somewhat contrary to expectations, these recipients usually do not have subnormal levels of CD4+ and CD8+ lymphocytes. However, they are typically B cell depleted, a condition that may protect them from late humoral rejection. Future directions will likely lead to the inclusion of important adjunctive agents having secondary anti-proliferative and anti-fibrogenic capabilities. Because chronic injury to renal allografts, as well as the dominant complications of renal transplantation such as cardiovascular disease and skin cancers, are woven together by a common theme of excessive proliferative activity, albeit of different cell types, long-term therapy will be directed at both protecting the allograft and the allograft recipient by incorporating as long-term therapy selected anti-proliferative agents that could include inhibitors of the renin-angiotensin-aldosterone system, statins, sirolimus, mycophenolic acid and leflunomide.

Acute Disease↗
PubMed2001

Laparoscopic bilateral synchronous nephrectomy for autosomal dominant polycystic kidney disease: the initial experience.

PURPOSE: We report our experience with laparoscopic bilateral synchronous nephrectomy for giant symptomatic autosomal dominant polycystic kidney disease (ADPKD) and compare outcome data with open bilateral nephrectomy. MATERIALS AND METHODS: Since March 1998, 10 patients underwent bilateral synchronous laparoscopic nephrectomy for giant symptomatic ADPKD. A 3 port retroperitoneal laparoscopic approach was used to secure the renal hilum and mobilize the kidney. Intact specimen extraction was performed through a midline infraumbilical extraperitoneal incision. The patient was then repositioned for the contralateral retroperitoneoscopic nephrectomy, with the second specimen also delivered through the same infraumbilical incision. Data were retrospectively compared with 10 patients who had undergone bilateral synchronous open nephrectomy for ADPKD between 1981 and 1992. RESULTS: Patients in the laparoscopic and open groups were comparable in regard to age (53 versus 47 years, p = 0.54) and Anesthesiologist Society of America class (3 versus 3, p = 0.84) but patients in the laparoscopic group were significantly more obese (body mass index 35.9 versus 23.8, p = 0.02). For comparable total specimen weights (3 versus 3 kg, p = 0.69) surgical time was longer in the laparoscopic group (4.4 versus 3.8 hours, p = 0.007). However, the laparoscopic group was superior in regard to blood loss (150 versus 325 cc, p = 0.05), postoperative requirement of nasogastric tube (10% versus 100%, p = 0.0001), narcotic analgesics (34.2 versus 120.4 mg. morphine sulfate equivalent, p = 0.03) and hospital stay (1.5 versus 9 days, p = 0.004). Complications occurred in 5 patients (50%) in the laparoscopic group and 4 (40%) in the open group (p = 0.66). No laparoscopic case was converted to open surgery. CONCLUSIONS: Synchronous bilateral retroperitoneal laparoscopic nephrectomy for giant symptomatic adult polycystic kidney disease is feasible, safe and efficacious, and can be performed either before or after renal transplantation. Compared to open surgery, the laparoscopic approach results in significantly shorter hospital stay, decreased morbidity and quicker recovery. Laparoscopy is currently our technique of choice in this setting.

Adult↗
PubMed2001

Renal outcome 25 years after donor nephrectomy.

PURPOSE: The extended outcome after kidney donation has been a particular concern ever since the recognition of hyperfiltration injury. Few published reports have examined donor renal outcome after 20 years or greater. Kidney transplantation has been performed at the Cleveland Clinic Foundation since 1963, at which there is extensive experience with live donor transplantation. We assess the impact of donor nephrectomy on renal function, urinary protein excretion and development of hypertension postoperatively to examine whether renal deterioration occurs with followup after 20 years or greater. MATERIALS AND METHODS: From 1963 to 1975, 180 live donor nephrectomies were performed at the Cleveland Clinic. We attempted to contact all patients to request participation in our study. Those 70 patients who agreed to participate in the study were mailed a package containing a 24-hour urine container (for assessment of creatinine, and total protein and albumin), a vial for blood collection (for assessment of serum creatinine) and a medical questionnaire. All specimens were returned to and processed by the Cleveland Clinic medical laboratories. Blood pressure was taken and recorded by a local physician. A 24-hour creatinine clearance and the Cockcroft-Gault formula were used to estimate renal function, and values were compared with an age adjusted glomerular filtration rate for a solitary kidney. RESULTS: Mean patient followup was 25 years. The 24-hour urinary creatinine clearance decreased to 72% of the value before donation. For the entire study cohort serum creatinine and systolic blood pressure after donation were significantly increased compared with values before, although still in the normal range. The overall incidence of hypertension was comparable to that expected in the age matched general population. There was no gender or age difference (younger or older than 50 years) for 24-hour urinary creatinine clearance, or change in serum creatinine before or after donation. Urinary protein and albumin excretion after donation was significantly higher in males compared with females. There were 13 (19%) subjects who had a 24-hour urinary protein excretion that was greater than 0.15 gm./24 hours, 5 (7%) of whom had greater than 0.8. No gender difference was noted in blood pressure, and there were no significant changes in diastolic pressure based on gender or age. CONCLUSIONS: Overall, renal function is well preserved with a mean followup of 25 years after donor nephrectomy. Males had significantly higher protein and albumin excretion than females but no other clinically significant differences in renal function, blood pressure or proteinuria were noted between them or at age of donation. Proteinuria increases with marginal significance but appears to be of no clinical consequence in most patients. Patients with mild or borderline proteinuria before donation may represent a subgroup at particular risk for the development of significant proteinuria 20 years or greater after donation. The overall incidence of proteinuria in our study is in the range of previously reported values after donor nephrectomy.

Adult↗
PubMed2000

Significant post-transplant hypogammaglobulinemia in six heart transplant recipients: an emerging clinical phenomenon?

BACKGROUND: The recent development of powerful agents such as mycophenolate mofetil and tacrolimus has altered current regimens for the prevention and treatment of allograft rejection. Questions have been raised about these newer regimens in terms of susceptibility to opportunistic infections and effects on host defenses. Severe hypogammaglobulinemia has been infrequently described in solid organ transplant recipients, but has been recently noted in six heart transplant recipients at one center, of whom five were receiving a combination of tacrolimus, mycophenolate mofetil, and prednisone. METHODS: Case summaries of six recent heart transplant recipients with total immunoglobulin G (IgG) levels of less than 310 mg/dl, five of whom had cytomegalovirus (CMV) infection and three of whom had multiple infections including Nocardia, invasive Trichophyton, and Acinetobacter bacteremia. Previous literature was reviewed with the aid of a Medline search using the search terms hypogammaglobulinemia; kidney, liver, heart, lung, and organ transplantation; mycophenolate mofetil; tacrolimus; cyclosporine; azathioprine; and nocardiosis. RESULTS: We here report six cardiac transplant recipients seen over a period of one year who were found to have immunoglobulin G levels of 310 mg/dl or below (normal: 717-1400 mg/dl). The first five patients were diagnosed because of evaluation for infections; the sixth, who was asymptomatic with an IgG level of 175, was found during screening for hypogammaglobulinemia instituted as a result of these first five patients. All six patients had received steroid pulses for rejection; all received mycophenolate mofetil; and 5/6 had been switched from cyclosporine to tacrolimus because of steroid-resistant rejection. Transient neutropenia (absolute neutrophil count less than 1000) was observed in 2/6; 3/6 had received OKT3 therapy for refractory rejection. These six patients were treated with a combination of antimicrobials, immunoglobulin replacement, and decrease in immunosuppressive therapy. CONCLUSION: The finding of unexpected hypogammaglobulinemia and concomitant infectious complications in six heart transplant recipients highlights a possible complication in a subset of patients receiving newer immunosuppressive agents. A larger prospective study is underway to determine risk factors for development of post-transplant hypogammaglobulinemia and to assess pre-transplant immune status of these recipients. Monitoring of immunoglobulin levels in high-risk patients receiving intensified immunosuppressive therapy for rejection may help to prevent infectious complications.

Acinetobacter Infections↗
PubMed1999

Chronic viral hepatitis in renal transplant recipients with allografts functioning for more than 20 years.

BACKGROUND: The impact of infection with hepatotropic viruses (hepatitis B virus [HBV] and hepatitis C virus [HCV]) on morbidity and mortality, and allograft function in renal transplant recipients with allografts functioning for >20 years is not known. METHODS AND RESULTS: Seventy-nine of 511 renal transplants performed at the Cleveland Clinic Foundation from January 1963 to January 1978 are known to have functioned for at least 20 years (level 5A). Fifty-four of these patients had hepatitis testing updated after their 19th year of transplantation. Fifteen patients had evidence of ongoing viral infection: persistent hepatitis B surface antigen in three (6%), HCV antibody (enzyme-linked immunosorbent assay II supplemented by recombinant immunoblot assay) in 11 (20%), and both viruses in one (2%). Of the 10 surviving patients, 8 were tested further for viral replication. HCV RNA (polymerase chain reaction; Amplicore) was positive in 6/7 (86%), and HBV DNA (hybridization) was positive in 1/2 (50%). An elevated alanine aminotransferase (>35 U/L) was present in all hepatitis patients, alpha-fetoprotein >10 ng/ml in 2/8 (25%), and cryoglobulins >50 microg/ml in 3/6 (50%) infected with HCV. No hepatocellular carcinoma was detected by hepatic ultrasound. In patients with chronic viral hepatitis, probable cirrhosis developed in 20% (3/15) compared to one patient in the group without hepatitis, but there was no mortality from liver failure in either group. Diabetes mellitus was significantly more common in those with than without hepatitis (11/15 vs. 10/39; P=0.002), but severe infection was not (9/15 vs. 15/39). Five hepatitis patients (33%) have died of non-hepatic causes (one from meningitis, one from unknown cause, and three from coronary heart disease [CHD] vs. only two individuals without hepatitis [5%]; P= 0.014). Although the more frequent occurrence of CHD among those with hepatitis was not significant (7/15 vs. 8/39; P=0.09), CHD as a cause of death in those with HCV was significantly increased (P=0.03). CONCLUSIONS: Twenty-year renal transplant recipients infected with hepatotropic viruses (HBV and HCV) have a high rate of active viral replication (88%), a greater frequency of diabetes (P=0.01), and a higher overall mortality (P=0.014).

Cause of Death↗
PubMed1997

The alloimmunized patient: monitoring and therapeutics.

The sensitization of renal transplant patients in the form of antihuman leukocyte antigen antibodies often constitutes significant risk to allograft function. Testing for these antibodies is done before, at the time of, and after renal transplantation. Correct interpretation of the results necessitates an understanding of the principles of the tests and of the clinical factors in the patients, especially those receiving another transplant. Treatment remains difficult, although preliminary trials with intravenous gamma globulin have shown promising results in some patients.

Cytotoxicity Tests, Immunologic↗
PubMed1996

De novo light-chain deposition disease in a cadaver renal allograft.

The deposition of immunoglobulin (Ig) light chains after renal transplantation most commonly occurs as a manifestation of recurrent multiple myeloma or recurrent light chain nephropathy. We report the development of de novo light chain deposition disease (LCDD) in a cadaveric renal transplant recipient 16 years after transplantation with no evidence of prior multiple myeloma or LCDD and no current evidence of myeloma or lymphoproliferative malignancy.

Adult↗
PubMed1995

The fate of renal allografts functioning for a minimum of 20 years (level 5A)--indefinite success or beginning of the end? A proposed classification of long-term allograft survivals.

Fifty-five renal allografts (44 from living-related and 11 from cadaver donors) that have functioned for at least 20 years (mean 22.9 +/- 2.3, range 20.1 to 30.7 years) were evaluated in three groups based on renal function: group I (n = 26), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl and no proteinuria; group II (n = 9), with a GFR of > or = 60 ml/min/1.73 m2 or serum creatinine < or = 1.4 mg/dl but > 150 mg proteinuria/24 hr; and group III (n = 20), with a GFR < 60 ml/min/1.73 m2 and/or serum creatinine > 1.4 mg/dL with or without proteinuria. Allograft factors, including acute rejection (AR) in 62% (34/55) and delayed function (DF) in 55% (6/11) of the cadaver grafts, did not preclude 20-year success and the prospect of continued survival since they were not significantly more frequent in group I, II, or III. However, AR was confined to a limited period within the first three months posttransplant in 18/18 recipients in groups I and II but only in 7/16 of group III (P = 0.0002). In groups I and II AR was treated with IVMP in 14/18 cases and only 6/16 in group III (P = 0.035). Donor age < or = 50 years and recipient age < or = 40 years each occurred in 87% (48/55) of these transplants. One- or two-HLA haplotype matching was present in 98% (43/44) of living related transplants. Major risks to the recipient were coronary artery disease (11 cases and 3 deaths), malignancy (18 cases and 1 death), and severe infection and hepatitis (35 cases and 3 deaths, 2 of whom also had coronary artery disease). Hypertension occurred in 25 recipients and diabetes mellitus in 12. Potential open-end success was compromised by renal dysfunction in groups II and III, but appeared possible in 12 of the 26 patients in group I. There is no apparent "safe-haven" point of time for immunosuppressed renal allograft recipients, who remain at increased risk for eventual renal allograft dysfunction, as well as cardiovascular, neoplastic, infectious, and metabolic diseases. In order to clarify and standardize the words "long-term," a simple classification of long-term allograft survivals is proposed.

Adolescent↗
PubMed1995

Changing demographics in renal transplant recipients: the 30 year Cleveland Clinic experience.

While it does appear that the most recent era of transplantation has not resulted in significant improvement in long-term allograft function, this appears to be due, at least in part, to the transplantation of increasing numbers of high-risk patients. It is noted that the improved results accomplished over prior eras of transplantation have been maintained despite the inclusion of these high-risk patients. Patients currently undergoing transplantation are more likely to be older, diabetic, obese or African American. All of these subgroups have poorer patient survival in the most recent transplant era and thus, death with a functioning graft has become a significant contributor to graft loss. Recipients were more likely to receive kidneys from cadaveric donors in the most recent era and within the live-donor groups, sibling donation has decreased. Hopefully, the recent trend of increased live-donor transplants (especially living, unrelated transplants) will continue. Cadaveric recipients were at higher risk for posttransplant ATN which, for the first time in the current era, had a significant adverse impact on graft survival. Long-term survival appeared to be associated with particular characteristics (optimal age at transplantation, optimal donor age, live donor, etc.), and can be achieved despite known risk factors, such as rejection or delayed graft function.

Adolescent↗
PubMed1994

Effect of HLA matching on organ distribution among whites and African-Americans.

A total of 159 patients received renal cadaveric grafts under 2 different allocation systems. System 1, a local variance (i.e., a point system different from that of United Network for Organ Sharing [UNOS]), and system 2, the current UNOS point system, differed in the relative emphasis on waiting time and HLA match. The racial composition of the donor pools and recipient waiting lists was the same for both periods examined. The percentage of African-Americans transplanted did not differ significantly under the 2 allocation systems and, in fact, increased slightly, from 29.4% to 33.8%, under system 2, which attributed more weight to HLA match. A difference in the allocation of kidneys from African-American donors was seen. Under system 1, only 2 of 8 kidneys from African-American donors went to African-American recipients, while under system 2, 6 of 8 kidneys from African-American donors went to African-American recipients. These data suggest that the current UNOS point system does not provide any added disadvantage to non-whites and may, in fact, provide an incentive for minority groups to donate organs, in that HLA matching appears to promote intraracial transplantation.

Black People↗
PubMed1994

Allocation of cadaver kidneys: new pressures, new solutions.

Equitable allocation of human cadaver kidneys is complex and challenging, both from the ethical and scientific points of view. It is based on the principles of distributive justice and medical utility. However, the optimal application of ethical principles will require further resolution of medical issues that currently focus on the number of transplants for a single patient, six antigen matches, lesser degrees of HLA matching, marginal recipients, various positive cross-match situations, and cold ischemia time. New HLA matching techniques and enhanced computer organ allocation systems have the potential to surmount racial differences and increase significantly the number of compatible renal allografts.

Cadaver↗
PubMed1994

Occult intracranial aneurysms in polycystic kidney disease: screening with MR angiography.

PURPOSE: To estimate the prevalence, location, and type of cerebral aneurysms in patients with adult polycystic kidney disease (PCKD) and identify associated risk factors. MATERIALS AND METHODS: Ninety-three patients with PCKD were screened for aneurysms with spin-echo parenchymal magnetic resonance (MR) imaging and three-dimensional time-of-flight MR angiography. Prevalence was estimated with the calculated proportions of patients who had aneurysms, adjusted for reported sensitivity and specificity of MR angiography. RESULTS: Thirteen aneurysms, found in 10 patients, were 7 mm or smaller in largest dimension; 11 of these aneurysms were saccular. Intra- and interobserver variabilities were 96%-98%. Conventional arteriograms, obtained in six patients, helped confirm the MR angiographic findings. The best estimates of prevalence of aneurysms were 11.7% in the study group (n = 93) and 25.8% in patients with a family history of aneurysms (n = 6). CONCLUSION: The prevalence of aneurysms in the study group was greater than in the general population. MR angiography is useful in screening for cerebral aneurysms.

Adult↗
PubMed1992

HLA molecules in autoimmune diseases.

The association of certain autoimmune diseases with HLA molecules is being refined through the use of sequence-specific oligonucleotide probes and amino acid sequencing, together with continuing elucidation of the functional features of HLA molecules derived from the milestone description by Bjorkman of the HLA molecular structure. The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain. In rheumatoid arthritis (RA) the HLA antigen association remains with certain Class II molecules of the DR series (DR4 and DR1) that share amino acid sequences with a restricted number of other DR antigens seen in RA, as well as a segment of the gp 110 protein of the Epstein-Barr virus. Although ankylosing spondylitis has a strong association with the Class I antigen B27, that association is not explained by any of the B27 subtypes defined by monoclonal antibodies, by the eight variable amino acids in B27 subtypes, or by the two unique amino acids on B27. The remarkable antibody cross-reactivity among lymphocytes bearing B27, a synthetic peptide sequence (63-84) of B27, and the 188-193 sequence of K. pneumoniae nitrogenase has provided strong support for molecular mimicry being an important mechanism in the association of HLA molecules with disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗