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.

Focal and segmental glomerulosclerosis. Immunohistologic study of 20 renal biopsy specimens.

To evaluate the deposition of immunoglobulins and complement and their relationship to sclerotic and nonsclerotic glomerular segments, immunoperoxidase without periodic acid-Schiff counterstain (IMP) and with periodic acid-Schiff counterstain (IMPAS) for IgG, IgA, IgM, and C3 was performed on cryostat-frozen sections using the direct method, along with routine light microscopy and electron microscopy, in a series of 20 renal biopsy specimens from 20 patients with the final diagnosis of focal and segmental glomerulosclerosis. Neither diffuse mesangial nor diffuse glomerular basement membrane deposits were detected by IMP, IMPAS, or electron microscopy. In 18 biopsy specimens, IMPAS demonstrated focal and segmental granular to globular deposits of IgM and/or C3 in sclerotic glomerular segments. In eight biopsy specimens, small granular deposits of IgM and/or C3 deposits were identified in optically normal glomeruli, suggesting that these deposits may precede segmental sclerosis.

Pregnancy after donor nephrectomy.

The use of living-related kidney donors has been a routine practice in most major transplant centers in the United States for more than 20 years. Concern has arisen regarding the potential for developing hypertension and progressive renal dysfunction after renal donation. Pregnancy results in hyperfiltration and might be an added risk for the development of hypertension, proteinuria, or renal insufficiency in donors. From 1963 until 1984, the Cleveland Clinic Foundation performed 1031 renal transplants, 355 from living donors. Of these 355 living donors, 191 were female, and of these, 23 successfully conceived after kidney donation. Prenatal and delivery records of all 23 were reviewed. There were 39 pregnancies in 23 women with 32 viable births. Conception ranged from 2 weeks to more than 9 years postnephrectomy. Mean blood pressure at the time of donor evaluation was 120/75 mm Hg (SD: +/- 11/8 mm Hg). Mean blood pressure during pregnancy was 114/68 mm Hg (SD: +/- 7/6 mm Hg). One plus proteinuria was detected in 2 women during the third trimester and trace proteinuria was seen in 7 pregnancies; this proteinuria disappeared after delivery. Thirteen of twenty women who carried to term were reevaluated 2-14 years after donor nephrectomy. All parameters studied were normal. Mean length of follow-up after donor nephrectomy was 7.9 years. These data suggest that, after donor nephrectomy, women can have a normal pregnancy without significant problems related to the kidney donation. Also, hyperfiltration associated with the combination of unilateral nephrectomy and pregnancy does not lead to significant hypertension, proteinuria, change in glomerular filtration rate, or abnormalities of the urinary sediment.

Bilateral emphysematous pyelonephritis.

Emphysematous pyelonephritis is a severe infection found almost exclusively in diabetics, characterized by the presence of gas within the renal parenchyma. The diagnosis is established radiographically. An additional case is added to the 52 cases reported in the literature; we believe this is the fifth reported case with bilateral emphysematous pyelonephritis. If appropriate diagnostic studies demonstrate no evidence of either perinephric abscess or urinary obstruction, intensive medical management should be the initial therapy for this condition. Surgical intervention is necessary in patients without prompt response to medical therapy.

Functional capacity and rehabilitation of recipients with a functioning renal allograft for ten years or more.

Forty-nine renal transplant recipients who had a single functioning allograft for ten or more years are reviewed. There were 17 cadaver recipients and 32 living-related recipients. Most patients have enjoyed excellent long-term renal function with stable mean daily dosages of azathioprine and prednisone. Fifty-three percent of patients never experienced a rejection episode, and 24% of patients experienced only one rejection episode. Five recipients (10%) developed malignancy following transplantation. Based on the Karnofsky activity scale, 80% of patients enjoyed unrestricted activity at ten years posttransplant. The two major factors contributing to declining activity were progression of systemic diseases such as atherosclerosis or diabetes, and declining allograft function. Following transplantation, all patients developed renewed interest in sexual activity, all men were potent, and all women experienced regular menses. Nine men achieved fatherhood and five women underwent successful pregnancy. Currently, 46 recipients are alive with a functioning allograft. These data confirm the ability of recipients with a long-term functioning renal allograft to return to the work force, participate in preillness levels of activity, and enjoy sexual activity and parenthood.

Determination of plasticizer levels in serum of hemodialysis patients.

Serum DEHP levels were measured on 27 hemodialysis patients at various time intervals. The following results were obtained: 1) Predialysis levels of DEHP occurred in only one of 22 samples. 2) Postdialysis serum levels reached a mean of 751 nGm DEHP/ml serum. 3) Samples from patients with less than 50 hemodialysis treatments gave a mean of 558 nGm/ml, while those with more than 50 treatments gave a mean of 973 nGM/ml. These numbers were found to be significantly different at a 95% confidence level. 4) No difference in DEHP levels were found for males and females. 5) The appearance of DEHP during dialysis and its disappearance after dialysis were found to be biphasic. 6) No correlation was found between serum DEHP and triglyceride levels in postdialysis serum samples.

Septicemia in renal transplant recipients.

Thirty-six renal transplant recipients with 47 episodes of septicemia were studied carefully at the bedside, in the laboratory, and, all too frequently, at autopsy. Gram-negative bacilli were the pathogens most commonly responsible, folloed in order of frequency by gram-positive cocci, polymicrobic etiologic agents, Listeria monocytogenes, and fungi. Infections of the transplant site (urinary tract or transplant wounds) caused septicemia in 51% of the cases. Other portals of entry included the lung, the abdomen, the meninges, the endocardium, and miscellaneous sites. The outcome of septicemia was fatal in 36% of the episodes. There was a significantly higher mortality for episodes of septicemia associated with pneumonia, persistent bloodstream infection, leukopenia, metastatic abscesses, clinical shock, and acute respiratory failure. The high mortality of septicemia in renal allograft recipients demands that extremely careful attention be given to subtle clinical clues denoting the onset and predicting the course of the disorder.