Dynamics of renal histamine in normal rat kidney and in nephrosis induced by aminonucleoside of puromycin.

Histamine is known to have a profound effect on capillary permeability in nonrenal tissues and this effect is presumably mediated by cyclic (c)AMP. Because in our previous experiments we found that histamine stimulates cAMP accumulation in glomeruli (Torres, V. E., T. E. Northryn, R. M. Edwards, S. V. Shah, and T. P. Dousa. 1978. Modulation of cyclic nucleotides in isolated rat glomeruli. J. Clin. Invest.62: 1334.), we now explored whether this amine is formed in renal tissue, namely in glomeruli, and whether its renal metabolism is altered in experimental nephrosis induced by puromycin aminonucleoside (PA) in rats. In normal rats, histamine content was higher (Delta + 240%) in cortex than in medulla. In glomeruli isolated from renal cortex, histamine content was significantly higher (Delta + 260%) than in tubules. Incubation of isolated glomeruli with l-histidine resulted in a time-dependent increase of histamine content in glomeruli, but no change was found in tubules. The increase in glomerular histamine was blocked by the histidine decarboxylase inhibitor bromocresine. In rats with PA nephrosis induced by a single intraperitoneal injection of PA (15 mg/100 g body wt) urinary excretion of histamine was markedly increased (>Delta + 200%), but control rats did not differ from rats with PA nephrosis in urinary excretions of l-histidine and of creatinine. At the peak of proteinuria (day 9 after injection of PA) the plasma level of histamine was slightly elevated, and plasma histidine slightly decreased in animals that developed PA nephrosis. The content of histamine was markedly higher and the level of histidine was significantly lower in the renal cortex of PA-nephrotic rats as compared with controls; PA-nephrotic and control rats did not differ in the content of histidine and histamine in the liver. In addition, the content of histamine was higher in glomeruli isolated from PA-nephrotic rats; lesser difference was found in cortical tubules. The results further indicate that PA-nephrotic rats have higher content of histamine in the renal cortex, predominently in glomeruli with increased urinary histamine excretion. The elevated renal cortical histamine is not due to higher availability of histamine precursor l-histidine. Results thus show that glomeruli are a major site of intrarenal histamine synthesis and accumulation, and also suggest that abnormal renal metabolism of this amine in PA nephrosis may be related, as a cause or as a consequence, to the pathogenesis of this disease.

Patterns of quantitative sensation testing of hypoesthesia and hyperalgesia are predictive of diabetic polyneuropathy: a study of three cohorts. Nerve growth factor study group.

OBJECTIVE: To test quantitative sensation testing (QST) patterns of hypoesthesia and hyperalgesia as indicators of diabetic polyneuropathy (DPN) and its severity RESEARCH DESIGN AND METHODS: We used Computer-Assisted Sensory Examination IV; characterized the QST results of the foot of each patient in three diabetic cohorts (approximately 1,500 patients) as hyperesthetic (< or = 2.5th percentile), low-normal (2.5th-50th percentiles), high-normal (50th-97.5th percentiles), or hypoesthetic (> or = 97.5th percentile); and tested associations with symptoms, impairments, and test abnormalities. RESULTS: Overall neuropathic impairment was most severe in the pancreas-renal transplant and nerve growth factor cohorts, but it was much less severe in the population-based Rochester Diabetic Neuropathy Study (RDNS) cohort. The frequency distribution of sensory abnormalities mirrored this difference. When the QST spectra of diabetic cohorts were compared with those of the control subject cohort for vibration and cooling sensations, the only abnormality observed was hypoesthesia, which was expressed as an increased number of subjects with values at or above the 97.5th percentile or by an increased percentage of cases with high-normal values. Symptoms and impairments of DPN were significantly more frequent in the subjects with values at or above the 97.5th percentile than in the subjects whose values were between the 50th and 97.5th percentiles. For heat pain (HP) sensation thresholds (intermediate pain severity [HP:5], pain threshold [HP:0.5], and pain-stimulus response slope [HP:5-0.5]), an increased frequency of both hypoalgesia and hyperalgesia was observed (especially in the RDNS cohort). Steeper pain-stimulus response slopes were significantly associated with sensory symptoms, including severity of pain. CONCLUSIONS: 1) Decreased vibratory sensation (hypoesthesia) appears to be characteristic of mild DPN, whereas panmodality hypoesthesia is characteristic of severe DPN. 2) A shift of vibratory and cold detection thresholds (and also of attributes of nerve conduction and a measure of autonomic dysfunction) from low-normal (2.5th-50th percentiles) to high-normal (50th-97.5th percentiles) appears to precede overt expression of DPN and to thereby provide evidence of subclinical abnormality 3) Heat stimulus-induced hyperesthesia (low thresholds) occurs especially in mild DPN, and, because it correlates with DPN symptoms and impairments, it must be attributed to hyperalgesia rather than to supersensitivity Therefore, hypoalgesia or hyperalgesia may be an indicator of early DPN.

Fanconi syndrome in adults. A manifestation of a latent form of myeloma.

From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded.

Percutaneous renal allograft biopsy. A comparison of two needle types and analysis of risk factors.

We retrospectively reviewed all (n = 369) percutaneous renal allograft biopsies performed at our institution between 1987 and 1992, comparing 14-gauge Franklin-Silverman (internal diameter = 2.0 mm, n = 169) and 18-gauge automated (internal diameter = 1.2 mm, n = 200) core biopsy needles. Visualization method, specimen adequacy, and complications were grouped by needle type. Five or more glomeruli were present in 88.9% of specimens obtained with Franklin-Silverman needles and in 82.7% with automated needles. A histologic diagnosis was obtained in 94.1% and 95.5% of Franklin-Silverman and automated biopsies, respectively. A complication was detected in 27 Franklin-Silverman biopsies (16.0%) and in 21 automated biopsies (10.5%) (not significant [NS], P > 0.05). Some procedures had more than one complication. Excluding asymptomatic gross hematuria, incidental hematomas, and incidental arteriovenous fistulas detected by routine ultrasonography, clinically significant complication rates were 6.5% for Franklin-Silverman biopsies and 2.5% for automated biopsies (NS). No allograft losses or patient deaths occurred as a result of allograft biopsy. Subgroup analysis of all biopsies performed with ultrasound marking alone (Franklin-Silverman, n = 119; automated, n = 148) revealed no significant (NS) difference in complication rates (15.1% vs. 10.8%). Additional subgroup analyses of palpation, ultrasound marking, and real-time ultrasonographic visualization techniques within each needle type also revealed no significant difference in the complication rate. Biopsy within 30 days of transplantation and no antihypertensive therapy were the only factors univariately associated (P < 0.05) with an increased complication rate. Multivariate analysis found biopsy within 30 days of transplantation (P = 0.007) was associated with the overall presence of one or more complications of any type. Type of needle (Franklin-Silverman vs. automated) achieved borderline significance (P = 0.047) when time to biopsy was statistically adjusted for; the Franklin-Silverman needle had a higher complication rate.

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.

Increased weakness after pancreas and kidney transplantation.

BACKGROUND: Already there is evidence that simultaneous pancreas and kidney (SPK), or pancreas after kidney (PAK) transplantation, in patients with type 1 diabetes mellitus and end-stage kidney disease prevents worsening of diabetic polyneuropathy, but neuropathic improvement is delayed and incomplete. METHODS: In 85 patients with type 1 diabetes mellitus who underwent SPK or PAK transplantations, we performed sequential neuromuscular evaluations before, every 3 months after, and yearly after transplantation, quantitating muscle weakness separately from overall severity of polyneuropathy. RESULTS: We found that, on average, the weakness subscore of the Neuropathy Impairment Score of the lower limbs [NIS(LL)-W] was significantly worse at 3, 6, 9, and 12 months (by about 5 points) than at baseline. By contrast, for these times after transplantation, a composite score of nerve conduction abnormalities, an independent measure of severity of polyneuropathy, was not significantly worse and, in fact, was significantly improved. In multivariate analysis, length of hospital stay correlated with the increased weakness. CONCLUSIONS: We conclude that: (1) increased neuromuscular impairment after transplantation is mainly due to muscle weakness and not to worsening polyneuropathy; (2) in multivariate analysis, duration of hospitalization after transplantation was significantly associated with this increased weakness; (3) increased weakness is probably due to development of myopathy, which may be related to graft rejection, immunosuppression, sepsis, and intercurrent infections; (4) in future transplantation trials, weakness should be evaluated separately from neuropathic status, and the lowest efficacious dosages of immunotherapy should be used; and (5) essentially all diabetic patients reported that SPK or PAK transplantation was worthwhile because it freed them from diabetic lifestyle concerns.

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

Hantavirus-specific IgG, IgM, and IgA in acute and chronic renal disease versus congenital renal disease in the United States.

In a blinded fashion, 165 serum samples from patients with biopsy-characterized acute and chronic renal diseases (ACRDs), 34 serum samples from patients with congenital renal diseases (CRDs), and 100 serum samples from healthy adults were assayed for immunoglobulin G (IgG), IgM, and IgA antibodies to Hantaan and Puumala viruses by enzyme immunoassay (EIA). Twenty-six percent (44 of 165) of ACRDs, 3% (1 of 34) of CRDs, and none (0 of 100) of the healthy serum samples were positive for hantavirus-specific antibodies (P < 0.001, Fisher's exact test). Thirty of 44 positive serum samples (68%) were from three groups: ie, acute tubulointerstitial nephritis (AIN), 20% (9 of 44); necrotizing glomerulonephritis (NG), 27% (12 of 44); and IgA nephropathy, 20% (9 of 44). The remaining 14 positive samples were from patients with a varied group of renal conditions. IgA antibody levels alone were elevated in 37%, IgG alone in 33%, IgM alone in 17%, and all three isotypes in 13% of the AIN-, NG-, and IgA-positive samples. These data indicate that three renal diseases account for approximately 68% of the hantavirus-positive sera tested and that serological evaluations should include all three isotypes of antibodies.

Cyclosporine elimination in the presence of TOR inhibitors: effects on renal function, acute rejection, and safety.

Sirolimus in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients when administered in double- or triple-therapy immunosuppressive regimens. Sirolimus administered as primary therapy has a beneficial effect on renal function, and the frequency of rejection episodes is similar to that of primary immunosuppression with cyclosporine. A strategy that may result in a more benign immunologic course with a substantially beneficial effect on renal function is to administer sirolimus and a calcineurin inhibitor early after transplantation, thereby promoting immunologic adaptation, and then to withdraw the calcineurin inhibitor at some point after transplantation to prevent nephrotoxicity. This article examines the results of this approach in recent studies that evaluated the effect of cyclosporine withdrawal on renal function, acute rejection, and safety in patients treated with sirolimus. Two open-label randomized trials of cyclosporine withdrawal were conducted in the United States, Canada, Europe, and Australia. In one of the studies, graft survival, patient survival, and the incidence of acute rejection at 6 months posttransplantation were not statistically significantly different between the patients receiving cyclosporine and the group that had undergone cyclosporine withdrawal. Furthermore, significantly better renal function was observed in the patients who underwent cyclosporine withdrawal compared with patients who continued to receive full-dose cyclosporine. These studies indicate that cyclosporine withdrawal has a beneficial effect on renal function without a significant increase in the incidence of acute rejection episodes.

Focal sclerosing glomerulonephropathy: a clinicopathologic study.

Forty cases of focal sclerosing glomerulonephropathy with nephrotic syndrome or proteinuria were studied retrospectively in regard to clinical presentation, response to steroid therapy and clinical course, and histopathology of the lesion. Morphologically there was a focal segmental and global sclerosis with subendothelial hyaline deposits, collapse of the capillary loops, intracapillary hyaline material or foam cells, filling and widening of the mesangium with mesangial matrix, focal tubular atrophy, and focal interstitial fibrosis. Thirty-four patients had been treated with prednisone; initial complete remission of the nephrotic syndrome occurred in only 4 patients and partial remission in 10. Nine of these 14 patients had nephrotic relapse or became resistant to steroids. Thirty-three percent of the patients progressed to end-stage renal failure and an additional 25 percent had impairment of renal function after a mean of 8 years from onset. Three patients received kidney allografts, and in two the disease recurred in the transplanted kidney. Focal sclerosing glomerulonephropathy associated with nephrotic syndrome or proteinuria appears to be a clinicopathologic entity characterized by resistance to steroid treatment, frequent progression to end-stage renal disease, and recurrence in the transplanted kidney.

Prospective study of anti-neutrophil cytoplasmic autoantibody tests in the diagnosis of idiopathic necrotizing-crescentic glomerulonephritis and renal vasculitis.

We prospectively assessed the value of anti-neurtrophil cytoplasmic autoantibodies (ANCA) and nuclear or perinuclear anti-neutrophil autoantibodies measured by indirect immunofluorescence microscopy and antimyeloperoxidase autoantibodies measured by a solid-phase assay in the diagnosis of idiopathic (pauci-immune) necrotizing-crescentic glomerulonephritis (NCGN) and renal vasculitis at our institution. A diagnosis was established on the basis of clinical and renal biopsy findings, and follow-up continued for at least 6 months. ANCA were measured at the conclusion of the study. Of the 111 study patients, 28 had NCGN and renal vasculitis. The immunofluorescence assay had 50% sensitivity and 79% specificity. The combination of the enzyme-linked immunosorbent assay for antimyeloperoxidase autoantibodies and the immunofluorescence assay for cytoplasmic ANCA had 78% sensitivity and 84% specificity. A firm diagnosis was established before the determination of ANCA in 26 of the 28 patients with NCGN and renal vasculitis. The antimyeloperoxidase autoantibody values would have suggested the diagnosis in the other two patients. Of these 28 patients, 5 had negative ANCA results. High antimyeloperoxidase autoantibody values were detected in patients with NCGN and renal vasculitis, whereas lower values were less specific and were detected mainly in patients with anti-glomerular basement membrane antibody disease and lupus glomerulonephritis.

Effects of systemic delivery of insulin on plasma lipids and lipoprotein concentrations in pancreas transplant recipients.

OBJECTIVE: To determine whether pancreas transplantation alters lipid and lipoprotein concentrations and whether peripheral hyperinsulinemia is always associated with altered lipid levels. DESIGN: We assessed the lipid profiles of seven pancreas-kidney recipients with insulin-dependent diabetes mellitus, seven kidney recipients without diabetes who received the same immunosuppressive agents, and eight normal subjects. MATERIAL AND METHODS: In the three study groups, fasting and postprandial plasma glucose, insulin, C-peptide, cholesterol, triglyceride, free fatty acid, and apolipoprotein A-I, A-II, C-II, and C-III concentrations were determined. RESULTS: Fasting and postprandial glucose concentrations did not differ between the two transplant groups; however, peripheral insulin concentrations were twice as high (P < 0.05) in the pancreas-kidney recipients as in the kidney recipients both before (102 +/- 15 versus 53 +/- 6 pmol/L) and after (123 +/- 22 versus 61 +/- 6 nmol/L per 6 hours) ingestion of a meal. Preprandial and postprandial insulin levels in both transplant groups also were greater (P < 0.05) than those in normal subjects (35 +/- 6 pmol/L and 40 +/- 7 nmol/L per 6 hours, respectively). Despite significant differences in insulin concentrations, no differences were noted in total cholesterol, high-density or low-density lipoprotein cholesterol, plasma free fatty acids, or apolipoprotein A-I, A-II, C-II, and C-III concentrations among the study groups. Plasma triglyceride concentrations in the two transplant groups were similar (114 +/- 20 versus 142 +/- 18 mg/dL) and were slightly more than those in the normal subjects (80 +/- 7 mg/dL). CONCLUSION: Despite peripheral hyperinsulinemia, pancreas transplantation can result in normal or near-normal lipid and lipoprotein concentrations. Thus, systemic delivery of insulin does not invariably produce an atherogenic lipid profile.

Pregnancy after pancreatic-renal transplantation because of diabetes.

In this article, we describe two pregnancies in the same patient after pancreatic-renal transplantation. Severe, labile hypertension necessitated delivery at 35 weeks during the patient's first pregnancy and at 30 weeks (associated with renal graft obstruction) during her second pregnancy. Women with insulin-dependent diabetes mellitus who undergo pancreatic-renal transplantation can have a successful pregnancy if adequate multidisciplinary, specialized medical care is rendered.

Acute intrinsic renal failure induced by indomethacin: role of prostaglandin synthetase inhibition.

Nonsteroidal anti-inflammatory agents are often used to treat acute inflammatory arthritis because of their effectiveness and the infrequency of reported serious side effects. This report describes two patients who had acute intrinsic renal failure that was triggered by indomethacin. Both patients were volume contracted and had other circulatory impairments. Azotemia was so severe as to require temporary hemodialysis in one patient. Intrinsic renal function began to recover within 5 days after discontinuation of indomethacin. At the time that recovery began, urinary prostaglandin excretion increased in both patients. A detailed review of pertinent experimental data indicates that renal production of prostaglandin is an important compensatory response that helps to maintain renal function in the face of diminished renal blood flow. Our cases provide clinical support for this hypothesis and illustrate the fact that indomethacin, by interfering with this protective mechanism, can lead to acute intrinsic renal failure. Clinicians must be aware of this possible complication and use the nonsteroidal anti-inflammatory drugs with caution in patients who have compromised prerenal status.

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.

Significance of proteinuria on the outcome of renal function in patients with focal segmental glomerulosclerosis.

Kidney survival analysis was performed for 64 patients with focal segmental sclerosis to ascertain whether the degree of proteinuria and other factors determined at the time of renal biopsy might be associated with progression to end-stage renal failure. On the basis of urinary excretion of protein, which was measured in 63 of the 64 patients, three groups of patients were identified: 15 patients (group A) had asymptomatic proteinuria (less than 3.5 g/24 h), 38 patients (group B) had nephrotic proteinuria (3.5 to 14 g/24 h), and 10 patients (group C) had massive proteinuria (more than 14 g/24 h). Kidney survival curves showed that the median time from biopsy to end-stage renal failure was more than 11, 7, and 3 years for groups A, B, and C, respectively. Thus, patients with massive proteinuria had an accelerated course to renal failure as compared with other nephrotic patients who had a lesser degree of proteinuria (P = 0.014) and patients who had asymptomatic proteinuria (P less than 0.001). Higher initial serum creatinine levels and severe tubulointerstitial damage were associated with a shorter time to end-stage renal failure. Age at onset and at biopsy, systolic and diastolic blood pressure, serum albumin and cholesterol, percentage of sclerotic glomeruli, mesangial proliferation, hyalinosis, vascular sclerosis, and initial response to prednisone were not associated with the time to end-stage renal failure when each of these variables was considered separately.

Treatment of severe nephrotic syndrome with meclofenamate: an uncontrolled pilot study.

The effect of meclofenamate on urinary protein excretion, level of serum albumin, and renal function was studied prospectively in 30 patients with corticosteroid-resistant severe nephrotic syndrome: 16 with focal segmental glomerulosclerosis, 12 with membranous glomerulopathy, and 2 with minimal-lesion nephropathy. Seventeen patients had a 40% or more reduction in urinary protein excretion ("responders"), and the decrease continued during long-term treatment. Meclofenamate therapy was discontinued after 2 months in eight "nonresponders" and in five other patients because of side effects (progressive increase in the level of serum creatinine in two, diarrhea in two, and pruritus in one). In responders, we recorded the following findings (mean +/- SD): urinary protein excretion decreased from 13.0 +/- 5.2 g/24 h to 7.2 +/- 3.5 g/24 h in 2 to 4 weeks and continued to decrease to 4.1 +/- 1.4 g/24 h at the time of the last follow-up study (median duration, 12 months; range, 6 to 36 months; P less than 0.01, 2 to 4 weeks versus later follow-up); the level of serum albumin increased from 1.9 +/- 0.5 g/dl to 2.9 +/- 0.7 g/dl (P less than 0.001) in 2 to 4 weeks; the level of serum cholesterol decreased from 413 +/- 125 mg/dl to 346 +/- 114 mg/dl (P less than 0.005) at the time of the last follow-up examination; and renal function remained unchanged from the baseline study to the follow-up study (serum creatinine 1.5 +/- 0.5 mg/dl versus 1.6 +/- 0.4 mg/dl and glomerular filtration rate 60.5 +/- 29.2 ml/min per 1.7 m2 versus 64.1 +/- 25.5 ml/min per 1.7 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Pancreas transplantation for the prevention of diabetic nephropathy.

Diabetic nephropathy is the leading cause of kidney failure in the United States. Poor glycemic control, hypertension, and smoking have been implicated as risk factors for the development and progression of diabetic nephropathy in patients with type 1 diabetes mellitus. Improved medical therapy including angiotensin-converting enzyme inhibitors and tight glycemic control with use of intensive insulin therapy have been shown to reduce the progression of diabetic nephropathy substantially based on albumin excretion rates. Despite these improvements in medical management, many patients still experience progression from early diabetic nephropathy to end-stage renal disease. Successful pancreas transplantation leads to normal glycemic control in patients with type 1 diabetes, but historically it has generally been limited to patients with both kidney failure and diabetes. In this review of the current treatment of diabetic nephropathy, we examine the potential role of preemptive pancreas transplantation in patients with diabetic nephropathy.