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Biomedical subjects

P P Frohnert

Publications and source records attributed to P P Frohnert.

At least 19 recordsLinked to original sources

The fate of renal transplants in patients with IgA nephropathy.

BACKGROUND: IgA Nephropathy (IgA N) is one of the most common glomerulopathies and may lead to renal failure in 10-20% of cases. After renal transplantation, IgA N has a strong tendency to recur in the graft. Initially considered a benign condition, graft losses from recurrent IgA N have been reported over the last 20 yr, casting doubt on the initial premise. Since large single-center studies of the fate of renal allografts in IgA N are rare and the Mayo Clinic transplant experience for IgA N is extensive (dating back to 1970), a review of these issues appeared worthwhile. METHODS: A retrospective study was done of all renal transplant patients who had had biopsy-proven IgA N as underlying disorder. We extracted data on the underlying disease, history leading to renal transplantation, factors affecting transplant outcome, and on the course after transplantation with special attention to rejection activity and recurrence of the primary disease. Standard statistical methods were employed. RESULTS: 53 renal allografts were transplanted to 51 biopsy-proven IgA N patients: 12 were cadaveric (CAD) grafts, 3 HLA-mismatched living related donor (LRD) kidneys, 29 one haplotype-matched LRD and 9 HLA-identical LRD organs. Five-year actuarial graft survival was 100% in HLA-identical LRD, 88% in one haplotype-matched LRD, and 74% in CAD grafts. All three HLA-mismatched LRD kidneys were functioning up to 1.6 yr (longest follow-up). Only one patient died after acute rejection of the CAD graft. There were 3 early graft losses from acute rejection and 4 late losses. IgA N recurred in 26% of allograft and led to significant loss of graft function in 10 of the 14 patients (71%) over a long period of observation. Three of four late graft losses were in patients with recurrent IgA N. Recurrence was not related to the type of graft, i.e. CAD vs. LRD, nor to the extent of HLA-matching in LRD transplantation. CONCLUSION: Renal transplantation in patients with IgA N has excellent patient and graft survival. There is a high rate of recurrence of the primary glomerulopathy in the renal allograft, and this event is by no means inconsequential. Loss of renal function and even graft loss occur over prolonged periods of time. There is no disadvantage getting a well matched LRD in regard to incidence of recurrent IgA N. Thus, we encourage LRD transplantation in IgA N.

Adolescent↗

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.

Adult↗

Noninvasive assessment of cardiac risk in insulin-dependent diabetic patients being evaluated for pancreatic transplantation using thallium-201 myocardial perfusion scintigraphy.

We examined the value of thallium-201 myocardial perfusion scintigraphy in noninvasive assessment of cardiac risk in 36 insulin-dependent (type 1) diabetic patients being evaluated for pancreas or combined pancreas/kidney transplantation. An extensive cardiovascular evaluation including electrocardiogram was performed in all patients, and most patients were also evaluated by two-dimensional and Doppler echocardiography. Exercise thallium studies were performed in 31 patients. Five patients were unable to exercise and underwent dipyridamole-thallium study. The thallium images were abnormal in 12 patients, 10 of whom underwent coronary arteriography. Significant coronary artery disease was found in 7 of these patients. Nineteen patients underwent pancreatic (3 patients) or pancreato-renal (16) transplantation without any occurrence of cardiac death or nonfatal myocardial infarction peri-operatively or on follow-up ranging from 7 months to 21 months. In contrast, 3 cardiac events occurred in 12 patients not approved for transplantation, each of whom had an abnormal thallium study exhibiting significant ischemia. Resting left ventricular global and regional function was not helpful in determining perioperative risk. Thus, thallium-201 myocardial perfusion scintigraphy may be useful in identifying diabetic patients at low risk for pancreas transplantation and may obviate the need for routine coronary angiography in these patients.

Adult↗

Pancreas transplantation at Mayo: I. Patient selection.

From October 1987 to December 1988, 59 patients underwent assessment for combined kidney and pancreas transplantation or pancreas transplantation after receiving a kidney allograft. We report our criteria for accepting candidates for transplantation, the results of the selection process, and the clinical and laboratory profile of those patients who underwent transplantation. Of the overall group, 22 patients (37%) were approved medically, 3 of whom were awaiting financial approval. Of the 59 patients, 15 (25%) were not approved for the transplantation program for medical reasons; in addition, 16 patients declined participation and 3 were not accepted because of lack of financial resources. Medical reasons for exclusion from pancreas transplantation were coronary artery disease in six patients, severe peripheral vascular disease in six patients, other medical problems in two patients, and noncompliance in one patient. Thus, many patients who underwent assessment for pancreas transplantation did not enter the program because of medical, financial, or personal preference reasons. In most cases, the medical reason for exclusion from pancreas transplantation was a cardiovascular disorder.

Adult↗

Pancreas transplantation at Mayo: III. Multidisciplinary management.

Although pancreas transplantation is a complicated procedure, a good level of success has been achieved because of the introduction of cyclosporine for immunosuppression, improved methods for diagnosing rejection, and a multidisciplinary approach to management. Our immunosuppressive regimen was quadruple therapy with induction by using Minnesota antilymphoblastic globulin. A biopsy technique was instituted in which the pancreas specimens were obtained under cystoscopic direction during episodes of hypoamylasuria. The criteria for rejection episodes were not only biochemical abnormalities but also histologic confirmation and a follow-up to exclude other causes of graft dysfunction. Infectious disease management included use of oral selective bowel decontamination for 3 weeks after transplantation. At the Mayo Clinic between October 1987 and December 1988, 16 patients received pancreaticoduodenal allografts (both kidney and pancreas in 13 and pancreas only in 3 after a prior successful kidney transplantation). In two pancreas and one kidney allograft, function was lost. One patient died of multiorgan failure. The cystoscopically directed biopsy technique was performed 23 times with minimal complications and a 93% success rate. The metabolic results have been excellent; the glycosylated hemoglobulin level was normal 3 to 6 months after transplantation. The quality of life was significantly improved in almost all patients. Nutritional assessment revealed little deterioration after transplantation. With a multidisciplinary approach, the needed answers about the effect of pancreas transplantation on the degenerative complications of diabetes should be forthcoming.

Adult↗

Chronic renal failure in non-insulin-dependent diabetes mellitus. A population-based study in Rochester, Minnesota.

STUDY OBJECTIVE: To identify the incidence of clinically defined chronic renal failure by clinical type of diabetes in a community diabetic incidence cohort, and to evaluate the relation between persistent proteinuria and chronic renal failure in non-insulin-dependent diabetes mellitus. DESIGN: Retrospective incidence cohort study. SETTING: Population-based in Rochester, Minnesota. PATIENTS: Residents of Rochester, Minnesota, with diabetes initially diagnosed between 1945 and 1979 who had follow-up to 1984 for clinically defined chronic renal failure. MEASUREMENTS AND MAIN RESULTS: Among 1832 persons with non-insulin-dependent diabetes who were initially free of chronic renal failure, 25 developed chronic renal failure (incidence, 133 per 100,000 person-years: CI, 86 to 196). The subsequent incidence of chronic renal failure among 136 insulin-dependent diabetic Rochester residents, three of whom developed chronic renal failure, was 170 per 100,000 person-years (CI, 35 to 497). After adjusting for potential confounding factors, we found that the risk for chronic renal failure associated with the presence of persistent proteinuria at the time of the diagnosis of non-insulin-dependent diabetes was increased 12-fold (hazard ratio, 12.1; CI, 4.3 to 34.0). When persistent proteinuria developed after the diagnosis of non-insulin-dependent diabetes mellitus, the cumulative risk for chronic renal failure 10 years after the diagnosis of persistent proteinuria was 11%. CONCLUSIONS: These population-based data suggest that most cases of chronic renal failure in diabetes occur in persons with non-insulin-dependent diabetes. These data also identify the increased risk for chronic renal failure among persons with non-insulin-dependent diabetes mellitus who have persistent proteinuria present at or developing after the diagnosis of non-insulin-dependent diabetes mellitus, such data may be useful for directing interventions to prevent or delay the development of chronic renal failure.

Cohort Studies↗

Twenty-five years of renal transplantation at Mayo Clinic.

1. Between 1963 and 1988, 935 patients received 1,082 renal transplants at Mayo Clinic. 2. Absolute and relative numbers of LRD grafts are declining. 3. Since accepting diabetic patients as suitable recipients in 1970, they account for over 20% of transplant activity. 4. Presence or absence of diabetes mellitus is the most important factor determining long-term (5 years) patient survival. However, in Period IV, (1983-1988), diabetes has not been an additional risk factor for graft survival. 5. Patient and graft survival of LRDs was better than CAD donors in all time periods. 6. With current immunosuppression since 1984, recipients of LRD primary grafts had a 97% patient survival at 4 years and those of CAD primary grafts, a probability of 84%. Primary allograft survival for LRD and CAD recipients was 90% and 68%, respectively, 4 years after transplantation.

Diabetes Complications↗

Epidemiology of persistent proteinuria in type II diabetes mellitus. Population-based study in Rochester, Minnesota.

Clinical risk factors for nephropathy were assessed in a population-based study of Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort). The 1031 Rochester residents with non-insulin-dependent diabetes mellitus (NIDDM) were followed through their complete medical records in the community to 1 January 1982. The prevalence of persistent proteinuria was 8.2% at the diagnosis of NIDDM. Among those initially free of persistent proteinuria, the subsequent incidence was 15.3/1000 person-yr. Twenty years after the diagnosis of diabetes, the cumulative incidence of persistent proteinuria was 24.6%. A proportional hazards model identified the following risk factors for persistent proteinuria in NIDDM: elevated initial fasting blood glucose (P less than .01); older age at onset of diabetes (P less than .01); male gender (P = .05); and presence of macrovascular disease (P = .05), diabetic retinopathy (P = .05), or glycosuria (P = .07) at the diagnosis of diabetes. Separate analyses controlling for attained age indicated no association between duration of NIDDM and the incidence of persistent proteinuria. Stratified analysis of the two most significant risk factors (fasting blood glucose and age) indicated that hyperglycemia was a stronger risk factor for proteinuria in younger diabetic subjects, perhaps because of a competing risk of death in the elderly diabetic patient. In contrast to a recently described decreasing secular trend of proteinuria in Danish insulin-dependent diabetes mellitus patients, there was no decrease over the past 40 yr in proteinuria risk in this NIDDM incidence cohort.

Adult↗

Graded exercise testing and training after renal transplantation: a preliminary study.

Aerobic exercise training has been used as part of the treatment for a variety of chronic disorders, most notably cardiovascular disease. In order to determine the feasibility and utility of regular exercise after renal transplantation, the responses of 10 patients to graded exercise testing were compared before training (T1), immediately after a program of supervised exercise training (T2), and a mean of 2.2 years after completion of the supervised program (T3). Supervised exercise sessions began a mean of 17 days postoperatively and continued for a mean of 5.5 weeks. Patients were encouraged to continue regular unsupervised exercise thereafter. All patients easily tolerated the supervised exercise sessions, which consisted of treadmill walking and cycle ergometry. Exercise capacity improved 90% between T1 and T2 and an additional 12% between T2 and T3. On the average, patients achieved a normal exercise capacity by 8 weeks after transplantation. Of the 10 patients, 7 had continued regular exercise training at T3. The observed increase in aerobic exercise capacity was probably related to improved renal function, an increased hemoglobin concentration, and the surgical healing process as well as the exercise training. We conclude that supervised exercise training for selected patients after renal transplantation is feasible and worthwhile.

Adolescent↗

Blood pressure determinants in living-related renal allograft donors and their recipients.

We studied 99 living related allograft donors with follow-up information of at least 10 years and the 50 recipients who had successful outcomes. Recipients were younger and had significantly lower blood pressures at follow-up than their donors. Borderline and definite hypertension were present in 22.2% and 4.0% of donors prior to donation, in 14.4% and 21.1% of donors at follow-up, and in 2.0% and 18.0% of the 50 recipients at follow-up. Age, relative weight, and mean arterial pressure (MAP) prior to donation were the key variables in predicting the follow-up ranked MAP of the donors. CPAH prior to donation was inversely correlated with the age of the donors and, indirectly, with the follow-up MAP. Donor CPAH prior to donation was significantly correlated with the renal allograft function of the recipients but not with the recipient ranked MAP at follow-up. No correlation of the ranked MAP or blood pressure outcome categories between donors and recipients was found. We conclude that donation of one kidney can accelerate the development of hypertension in those donors with predisposition to develop hypertension. In addition, the predisposition of the donors to develop hypertension and their age, within the range observed in the study, does not significantly influence the long-term blood pressure status of the recipient.

Adult↗

The risks of unilateral nephrectomy: status of kidney donors 10 to 20 years postoperatively.

We received requested follow-up information from 105 (73%) of our 144 kidney donors who had undergone unilateral nephrectomy 10 to 20 years previously. Five donors had died of unrelated causes 6 or more years postoperatively. Studies in the remaining 100 donors showed that the current mean serum creatinine concentration was 1.2 mg/dl and the mean 24-hour urinary protein value was 89 mg. Hypertension (defined as 160 mm Hg or more systolic, 95 mm Hg or more diastolic, or both) was present in 19% of the donors. In a subgroup of 66 donors who had had serial serum creatinine determinations, the renal function, as estimated on the basis of these serum creatinine values, had not deteriorated with time. Thus, we consider unilateral nephrectomy in this group of patients relatively safe. Subsequent evaluation will be necessary to ascertain whether these findings prevail.

Adolescent↗

Meclofenamate treatment of recurrent idiopathic nephrotic syndrome with focal segmental glomerulosclerosis after renal transplantation.

Recurrent corticosteroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis (FSGS) caused the failure of a first renal allograft in a 41-year-old man. Recurrence of the nephrotic syndrome in the second renal allograft was successfully controlled by the administration of meclofenamate, and the renal function has remained stable for 2 1/2 years. No accepted treatment is available for corticosteroid-resistant nephrotic syndrome with FSGS. This report suggests that administration of meclofenamate might be beneficial in some patients with corticosteroid-resistant nephrotic syndrome and FSGS. Because of the potential side effects, however, careful supervision of this therapy is of the utmost importance.

Adult↗

Improving results in primary diabetic renal transplantation.

One hundred seventeen patients with renal failure resulting from insulin-dependent diabetes mellitus received primary renal allografts from June 1970 to April 1983. Factors significantly associated with improved graft and patient survival were LRD sources (in particular, HLA-identical) and splenectomy. Variables such as transfusions, age, sex, and the administration of ALG were not significantly associated with transplant outcome. However, survival of patients and grafts has improved in recent years and continues to compare favorably with hemodialysis results. Although splenectomy might be the most important variable responsible for the improvement of our recent results, the use of ALG for rejection episodes might have contributed substantially to the improvement. Early transplantation, not analyzed in this study, might prove to be the most significant variable in the outcome of transplantation in patients with diabetic renal failure.

Adult↗