Lars Frödin

Ischemic heart disease - major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively. Of deaths with a functioning graft, 53% were due to ischemic heart disease (IHD) and 10% were due to other vascular disease. In the 55− to 64-year-old age group, the risk of death from IHD was 6.4 times higher in the transplanted nondiabetic patients, 8.6 times higher in the dialysis patients (European Dialysis and Transplant Association figures), and 20.8 times higher in the transplanted diabetic patients than in the general population (national figures). A multivariate Cox regression analysis showed that old age, diabetes mellitus, occurrence of acute rejection, pretransplant transfusions, delayed onset of graft function, and male gender were significant for death in IHD. We conclude that, in comparison to reports from other regions, Scandinavian renal transplant recipients are at high risk of dying of HID. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

T‐Lymphocyte Subsets and HLA‐DR‐Expressing Cells in Rejected Human Kidney Grafts

This communication describes an immunohistochemical analysis of rejected human renal allografts. T‐lymphocyte subsets were identified in frozen tissue sections, by Leu 1 (anti‐ ‘pan’ T lymphocytes). Leu 2a (anti‐ ‘cytotoxic/suppressor’ T cells), and Leu 3a (anti‐ ‘helper/inducer’ T cells) monoclonal antibodies. In addition, HLA‐DR‐positive cells were identified by simultaneous labelling with heterologous anti‐HLA‐DR antibodies. T cells dominated the cellular infiltrates in acute cellular rejection. Leu‐3a‐positive cells were more numerous than Leu‐2a‐positive cells. The Leu‐3a‐positive cells usually appeared in clusters, whereas the Leu‐2a‐positive cells appeared scattered in the tissue. HLA‐DR‐positive non‐T cells were found within clusters of T ‘helper/inducer’ cells. The cell pattern shares many features with the findings in detayed‐type hypersensitivity reactions.

Safety Aspects and Diagnostic Findings of Serial Renal Allograft Biopsies, Obtained by An Automatic Technique with a Midsize Needle

Percutaneous biopsy is an important diagnostic procedure in evaluating the renal allograft with compromised function. Graft losses and haemorrhagic complication are major risks. To minimize these problems we used a midsize TruCut needle, controlled by an automatic firing device (Biopty-Cut), fixed to an ultrasound guidance system. Core biopsies of 1.2 x 20 mm were obtained from 1,421 kidney grafts. On 5 occasions a haemorrhagic complication that required prolonged hospitalization or intervention occurred. No grafts were lost as a consequence of the biopsy procedure. Typical histological morphological parameters found during allograft rejection has earlier been established. Using a protocol with 27 histological parameters this study confirms that recognized criteria for rejection can be relied upon even with this smaller needle. The results showed that the degree of oedema and lymphocytic infiltration of the interstitium and in the arterial wall discriminated best between rejecting grafts and non-rejection grafts.

Prospective study of calcium homeostasis after renal transplantation.

Abstract. Nineteen consecutive patients receiving renal transplants underwent prospective evaluation of their calcium homeostasis for 1 year after transplantation to characterize indices of hyperparathyroidism (HPT) amelioration. All but one underwent dialysis, and six had vitamin D supplementation before grafting. The rapid falls in serum creatinine concentrations and increased creatinine clearances the first weeks after grafting were accompanied by rapidly reversed hypercalcemia and hypermagnesemia, induced hypophosphatemia, maintained parathyroid hormone (PTH) excess and calcitriol deficiency, and decreased alkaline phosphatases. At 3 months when the serum calcitriol had started to rise, serum PTH levels were the lowest and parathyroid responses to induced hypocalcemia the least abnormal. This was coupled to peaks in serum calcium, 24-hour urine calcium excretions, and serum alkaline phosphatase levels. All patients had subnormal creatinine clearances at the study end, and normal serum PTH occurred in only seven of them. Arbitrary subgrouping of the material was performed according to posttransplant creatinine clearance and serum PTH levels. More satisfactory graft function related to lower serum PTH values and less abnormal parathyroid responses to induced hypocalcemia, earlier and higher rises in serum calcitriol, and higher urine calcium excretion. Patients with mild HPT at the study end generally had higher creatinine clearance, lower serum PTH, calcium, and alkaline phosphatase values, and lower urine calcium excretion. Moreover, they had fewer prevalent signs of radiologic bone involvement before grafting. These temporal diversities in conjunction with the variable graft function and intensity of immunosuppression provide a complex interaction in renal transplant recipients, which should be considered in the light of improved function of the PTH/PTHrP receptor in bone and kidney and cation receptors in the parathyroid and kidney.

Tissue Distribution of T‐Lymphocytes and Ia‐Expressing Cells in Rat Kidney Grafts

In a rat kidney transplantation model, DA kidneys were transplanted into Lewis rats. Syngeneic Lewis transplantations were studied as controls. Histologic evaluation was made, and immunohistochemical staining with a single‐staining peroxidase–antiperoxidase technique on frozen sections was performed after 2, 4, 6, and 8 days. Antibodies for Ia antigen (Ox 6), ‘suppressor/cytotoxic’ cells (Ox 8), pan‐T cells (W 3/13), and ‘helper/inducer’ cells (W 3/25) were used. Allogeneic grafts were almost completely rejected in 8 days. Syngeneic grafts also showed lymphocyte infiltrates, somewhat later than allogeneic ones, but were not rejected. In these infiltrates W 3/25‐positive cells dominated, being even more numerous than W 3/13‐positive cells. Relatively fewer Ox 8‐positive cells were seen in the infiltrates of syngeneic than in allogeneic transplants. Infiltrates occurred later in the renal medulla than in the cortex. Perivascular infiltrates with cells of all investigated phenotypes were seen earlier in allogeneic grafts than in syngeneic ones. All tubular cells within one renal tubule appeared either Ox 6‐positive or ‐negative. With time, all tubules in the allogeneic transplants became Ox 6‐positive. Some increase of Ox 6‐positive tubules was also seen in syngeneic transplants.

A randomized multicenter trial of cyclosporin and prednisolone versus cyclosporin, azathioprine, and prednisolone following primary living donor renal transplantation

A total of 195 consecutive recipients of primary living donor renal transplants were randomized to receive either cyclosporin (CyA) and prednisolone (double therapy) or CyA, prednisolone, and azathioprine (triple therapy). There was no significant difference in patient or graft survival, incidence of acute rejection episodes, or major complications between the groups. The graft survival at 5 years was 71.5% in patients receiving double therapy and 71.6% in patients receiving triple therapy. In a Cox regression analysis, recipient age and occurrence of acute rejection were the only independently significant variables affecting graft survival, whereas treatment schedule did not. Renal function was stable throughout the observation period and did not differ between the double and triple therapy groups. A linear regression analysis showed that recipient age, donor age, gender, and occurrence of acute rejection significantly influenced the serum creatinine level. This and previous similar prospective studies in cadaveric renal transplantation indicate that there is no advantage of routinely adding azathioprine to a double drug regimen.

Preanastomotic Arterial Stenosis in Renal Transplant Recipients: A Report of Four Cases

Four cases of arterial stenosis proximal to the renal artery anastomosis in renal transplant recipients are described. In three of the cases infarcts also occurred in the transplanted kidney. The stenoses were probably caused by injury from a vascular clamp. Embolisation from the injured area of the vessel was probably responsible for the infarcts. The radiological findings were characteristic in the three cases thus examined. The importance of special care in handling the blood vessels is stressed. Detailed angiographic studies are required to ensure diagnosis.

Surgical Treatment of Hydronephrosis by the Anderson-Hynes Method

During the period 1959–1968, 23 patients underwent surgery by the Anderson-Hynes technique for hydronephrosis. In 18 patients no mechanical cause of the disease was found, and 16 of these patients were followed up over a long period of time. The results, evaluated from subjective symptoms, occurrence of urinary tract infection and prolonged urography, were good.

Computed tomography, ultrasonography and gamma camera scintigraphy after renal transplantation.

In routine postoperative observations on 31 transplanted kidneys, computed tomography (CT), ultrasonography (US) and gamma scintigraphy (GS) were compared with respect to diagnosis of abscess or lymphocele in the vicinity of the transplant, rejection and outflow obstruction. The results showed that US was the most reliable procedure for detecting fluid-filled cavities. In cases of graft rejection, GS was of most value. In demonstrating outflow obstruction, there was no definite difference between the three methods.

Renal transplantation in Uppsala.

The history and progress of organ transplantation in Uppsala are reviewed. Renal transplantation was begun in 1969, and the programme now comprises 50 to 60 transplants per year. Since 1976 the operation is performed at the department of urology. Close collaboration has been established with other departments in the hospital, especially with the medical nephrology unit. The indications for active management of uraemic patients have broadened, and maintaining resources on a par with the demands has constantly been a problem. This report concerns immunosuppressive therapy, transplantation results and research connected with the transplantation programme and deals briefly with the prospects for Uppsala as a transplantation centre in the future.