Outcome of patients with secondary amyloidosis in dialysis treatment.

Between the years 1974 and 1987, 37 patients with secondary amyloidosis entered dialysis treatment at our department. All had amyloidosis secondary to chronic arthritic disease (35) or to other chronic inflammatory causes (2). Only two patients were maintained on CAPD throughout follow-up; 12 patients (32%) received a kidney transplant. Survival in dialysis at 1 year was 82%, at 2 years 46%, and at 3 years 37%. Survival of amyloidosis patients transplanted at the Finnish transplant centre within the same period was worse at 1 year, but better at 2 and 3 years, 70%, 62%, and 62% respectively, but the difference was not significant. Populations are not compatible, since patients were selected for transplantation. Infection was a common cause of death, 7/18 (39%) deaths; cardiac deaths were less common, only two myocardial infarctions and one cardiac arrhythmia (17%). Symptoms of cardiac amyloid infiltration indicated a poor prognosis, although it did not necessarily predict death of a cardiac cause. Cardiac infiltration of amyloid was more common in autopsy than previously reported (10 of 13 patients), probably indicating longer duration of amyloidosis in patients treated with renal replacement therapy. Patients who died within follow-up had a shorter interval between the start of primary disease and the development of amyloidosis than those who survived, 11.8 versus 17.7 years (P = 0.041), and also a slightly shorter period between diagnosis of amyloidosis and start of dialysis, 3.0 versus 4.4 years (P = 0.129). This indicates that the rate of progression of amyloidosis determines the development of disease-associated complications, and fast progression may predict serious outcome.

Results of kidney transplantation in patients with diabetic nephropathy.

The success rate of transplantation in diabetic patients was acceptable, and short-term patient survival was similar for diabetic and nondiabetic patients. Later clinical outcome of diabetic patients was rather poor due to advanced disease-related complications.

Outcome of patients with diabetic nephropathy after kidney transplantation.

During the period 1973-1983, 1,014 patients with end stage renal failure received a kidney graft at the Helsinki University Central Hospital. As a consequence of diabetic nephropathy, 163 of them (16%) developed renal failure. Ten diabetic (6%) and 72 non-diabetic (9%) patients received grafts from a living donor. One-year patient survival did not differ between diabetic and non-diabetic patients (76% and 79%, respectively). From the second post-transplant year onwards patient survival was worse in diabetic than in non-diabetic patients. The two groups did not differ with respect to graft survival. Sixty-two diabetic patients (38%) died during the follow-up period, with myocardial infarction as the most common cause of death (31%), followed by infection (15%) and cerebral stroke (13%). Seven myocardial infarctions out of 19 occurred within three months of transplantation. However, significantly more fatal and non-fatal myocardial infarctions were observed in post-transplant patients who had returned to dialysis therapy than in patients with a functioning kidney graft. Blindness did not influence the outcome of transplantation. Nor did the transplantation significantly affect the course of this diabetic complication. In conclusion, although the early success rate of kidney transplantation in our study population was acceptable, the later outcome was poor, mainly due to advanced disease-related complications.

Renal transplantation in 45 patients with amyloidosis.

The results of renal transplantation in patients with amyloidosis were studied in 45 patients receiving primary cadaver grafts at a single center between March 1973 and October 1981. A control group of 45 patients with glomerulonephritis receiving primary cadaver grafts during the same period was also studied. These were matched according to the number of A and B locus incompatibilities and the date of transplantation. The 3-year survival of the patients with amyloidosis was statistically significantly inferior (51%) to that of the controls (79%). Age over 40 years was the major factor determining low survival in these patients. Mortality was concentrated in the early posttransplantation period. The 3-year graft survival rate was the same in amyloidotics (38%) and controls (45%); with death of patients not included in graft loss, the corresponding figures were 53% and 49%. Appearance of amyloid in the transplant was established by biopsy in four patients at 11-37 months of follow-up. Renal transplants functioning for more than one year were calculated to incur a minimum risk of 20% of acquiring amyloid.

Radiological progression of rheumatoid arthritis in renal transplant recipients.

Radiological progression of rheumatoid arthritis (RA) was evaluated retrospectively in eight patients with amyloidosis secondary to classical or definite RA and successful renal transplantation. Wrist joints, metacarpophalangeal, proximal interphalangeal, and metatarsophalangeal joints were graded on a scale from 0 to 5. The annual progression rate was calculated separately for the time before and after transplantation. A slight acceleration of the progression was observed after transplantation and is assumed to be due to activation of the rheumatoid disease when the azotaemia was corrected.

Aseptic necrosis of the femoral head following renal transplantation.

The occurrence of aseptic hip necrosis was investigated in 546 renal transplant patients (639 transplants) with graft survival for a minimum of 12 months. Aseptic hip necrosis developed in 39 hips in 29 patients (5.3%) from 3 to 121 months (mean 22 months) after the renal transplantation. There was no sex-related difference in incidence of hip necrosis. The complication was significantly more common among patients younger than 20 than among those older than 40 years. The development of hip necrosis did not correlate with type of renal disease, origin of graft (cadaver of living relative donor), side of transplant or length of dialysis treatment. The number of transplantations per patient did not influence the occurrence of hip necrosis. Analyses of serum concentrations of creatinine, calcium, phosphorus and parathormone before and at different periods after transplantation revealed no patterns predictive of hip necrosis. The pathogenesis of aseptic necrosis of the femoral head obviously is multifactorial.

Renal allograft glomerulonephritis.

The analysis of 1282 renal transplantations revealed 14 cases of allograft glomerulonephritis (GN). Membranous GN was found in seven patients, in four of whom the GN appeared de novo. IgA GN was evident in three cases and focal segmental glomerulosclerosis and mesangiocapillary GN type 1 in two cases each. The signs of GN were detected 0.5-72 months after transplantation. The most common clinical sign indicating an allograft biopsy was nephrotic syndrome. Deterioration of the graft function was often seen and it was usually associated with chronic rejection.

Steroid treatment and aseptic necrosis of the femoral head in renal transplant recipients.

The subject of our study was 546 renal transplant recipients with a graft survival for minimum 12 months. Of these, 29 renal recipients (5.3%) developed aseptic necrosis of the femoral head. The examination revealed that there were no significant differences between the renal recipients with hip necrosis and the control group in the total quantities of administered glucocorticosteroids, whereas there was a highly significant correlation between the two groups in the number of the intravenously administered methylprednisolone pulse doses.

Glomerulonephritis in renal allografts: results of 18 years of transplantations.

The analysis of 1282 renal transplantations revealed 13 cases of allograft glomerulonephritis (GN). Membranous GN was detected in seven patients, and mesangiocapillary GN type 1, IgA GN and focal segmental glomerulosclerosis in two patients each. The transplantation material included 13 patients with post-transplant nephrotic syndrome (NS), in 9 of whom it was evidently caused by GN. NS was the most common clinical sign of allograft GN. In addition, one patient developed low-grade proteinuria and one hematuria. In one case no signs of GN were detected at the time of graft biopsy. Loss of allograft function was associated with additional severe rejection changes. Five patients are living with a functioning graft, four have been started on hemodialysis and four have died form non-renal causes. It is concluded that NS is rare after renal transplantation and that it is most often caused by allograft GN. The prognosis of the graft is determined by co-existing rejection.

Serum ascorbic acid in patients undergoing chronic hemodialysis.

Serum presupplementation ascorbic acid levels were subnormal in 8 out of 10 patients undergoing chronic hemodialysis with capillary film and capillary flow dialyzers, the mean duration of treatment being 11 months. Supplementation with 100 mg ascorbic acid daily for two weeks raised the ascorbic acid values to normal in 9 out of 10 patients. After supplementation with 500 mg daily, all patients had ascorbic acid levels exceeding the normal upper limit, and 3 of them had gastrointestinal side-effects. The mean blood pH value, measured in 24 patients on chronic hemodialysis, showed a significant, though slight, decrease during supplementation with 500 mg daily as compared with the mean presupplementation value, but no statistically significant changes were observed in blood bicarbonate, base excess or PCO2 values.

Ultrasonic scanning after percutaneous renal biopsy.

Renal ultrasonic scanning was performed before and after 57 consecutive kidney biopsies in order to assess the value of this method in the diagnosis of complications. One large and six small perirenal haematomas were found, corresponding to an incidence of 13%. This figure is considerably larger than the incidence found with conventional diagnostic methods, but smaller than with computed tomography. One hydronephrosis and a blood clot in the urinary bladder were also diagnosed. No clinically significant complications were missed. We recommend ultrasonography as the first diagnostic procedure when biopsy complications are suspected.

Recurrence of renal amyloid and de novo membranous glomerulonephritis after transplantation.

Eleven patients with amyloidosis were treated for terminal renal failure by transplantation, receiving 12 cadaver allografts. In one patient the amyloidosis was primary and in the remaining 10 it was secondary to a chronic inflammatory disease. All of the patients were subjected to one or two fine-needle aspiration biopsies of the kidney graft during a followup of 11 to 68 months. The biopsies of three patients, one with primary amyloidosis and two with ankylosing spondylitis, revealed amyloid recurrence in the graft. These recurrences were diagnosed at 11, 28, or 37 months, respectively. The risk of amyloid recurrence is thus by no means negligible. The present study revealed no factors determining the development of recurrence. In two additional cases, membranous glomerulonephritis was observed in transplant biopsy. Both of these patients had rheumatoid arthritis as the underlying disease and were treated with gold salts before transplantation. It is suggested that an impaired immune response, related to amyloidosis and/or immunosuppressive therapy, may have favored the formation and deposition of circulating immune complexes.

HLA-antigen distribution in juvenile diabetics with end-stage nephropathy.

Diabetic nephropathy with renal failure is a major cause of death among juvenile diabetics. It is as yet unknown why some diabetics suffer from this serious renal complication while others do not, in spite of long duration of diabetes. For therapeutic reasons it is of the utmost importance to find out which patients are at risk long before the manifestation of renal insufficiency. Juvenile diabetics are know to have an increased frequency of some HLA antigens. The relationships between the HLA-A, HLA-B and HLA-C antigens and diabetic end-stage nephropathy were therefore evaluated in the present study. The study comprised 121 insulin-dependent diabetics with renal failure (mean age at onset of diabetes 13.4 leads to 7.6 (SD) years, mean pre-uraemic duration of diabetes 21.7 leads to 4.7 years), and 36 insulin-dependent diabetics (mean age at onset of diabetes 16.5 leads to 8.4 years) without renal failure despite long mean duration of diabetes (32.5 leads to 5.1 years). We found the expected significant increase in B8 and B15 and a decrease in B7 frequencies in the diabetics compared with the non-diabetic population, but no difference was found between uraemic and non-uraemic diabetics. Neither the early onset of diabetes nor the rapid appearance of renal failure was associated with any HLA frequency. The data therefore do not provide evidence of the involvement of B8 or B15 allele-associated mechanisms in the disease process leading to diabetic nephropathy with renal failure. There was a significant difference (p corrected less than 0.01) between the frequency of Bw22 in uraemic diabetics (14%) and that in non-diabetics (5%) while the frequency was near normal in non-uraemic diabetics. Further data are needed to confirm the possible association of Bw22 with diabetic nephropathy.

Effect on patient and graft survival of reducing the methylprednisolone dose after renal transplantation.

In 1972-1979, 584 first renal transplantations were carried out. During the period 1972-1975, methylprednisolone was given for the first six months after the transplantation in a total dose of about 9 g, in addition to the usual dose of azathioprine (period 1). In 1976-1979 the total dose of methylprednisolone given during a corresponding period of time was about 4.5 g (period 2). Cutting down the dosage to half resulted in an improvement of the one-year patient survival by 16 per cent (from 63 to 79 per cent and the one-year graft survival by 10 percent (from 46 to 56 per cent).

Renal transplantation with living donor.

In 1967-1980, 134 renal transplantations with living donor were carried out. Eleven transplantations were done on children under 15 years old, 6 on patients over 50. The remainder were 15-50 years old. Twenty-three patients died. The patient survival was 92 per cent after one year, 76 per cent after 5 years and 54 per cent after 10 years. Graft survival was 84 per cent after one year, 68 per cent after 5 years and 48 per cent after 10 years. Psychological and psychiatric problems as well as legal and economic aspects of the donor's situation are discussed.

Kidney transplantation and tumours.

During the period 1964--1978 700 renal transplants were given to 602 patients. Eight patients had a history of tumour before transplantation. After transplantation six cases with a de novo tumour were found. The treatment of the pretransplant tumours was completed on average 3 years before transplantation. The average interval from transplantation to discovery of de novo tumour was 2 years. The pretransplant tumours appeared 5 to 9 years before last control (Jan. 79) (mean 8 years). Two of the transplanted patients with previous tumours died later of their tumours. The others are still alive. Two of the patients with de novo tumour died of vascular accidents and one of tumour. The other three are alive. It seems that transplantation can be successful in patients with previous tumours. This study does not support previous reports of increased risk of de novo tumours in transplanted patients.