Kidney transplantation--a 46-year experience from the Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.

The limiting factor in organ transplantation is the availability of organs. Ongoing work to improve donation rates both at the public and the organizational level in donating hospitals is essential. We also think that encouragement of live donation is important, and the possibility of ABO incompatible transplantation has increased the number of LD transplantations. The one-year graft survival rate is excellent and focus has shifted towards achieving long-term results to reduce the attrition rate. There is also an increasing interest in studying and working to reduce comorbidities on a long-term basis and thus, improve survival rates and recipient quality of life.

Conversion from calcineurin inhibitor to either mycophenolate mofetil or sirolimus improves renal function in liver transplant recipients with chronic kidney disease: results of a prospective randomized trial.

BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant cause of morbidity and a risk factor for mortality after orthotopic liver transplantation (OLT). The use of calcineurin inhibitor (CNI)-based immunosuppression is an important etiologic factor for developing CKD. CNI discontinuation or minimization protocols with replacement of the CNI with non-nephrotoxic drugs, such as mycophenolate mofetil (MMF) or sirolimus (SRL), may have the potential to preserve or recover renal function. PATIENTS AND METHODS: In this prospective, randomized, single-center study with CNI discontinuation, OLT recipients with CKD (measured glomerular filtration rate [GFRm] 15-45 mL/min/1.73 m(2)) were randomized to either SRL or MMF-based immunosuppression. The main objective was to study the effect of CNI discontinuation on renal function. Secondary aims were to assess the frequency of biopsy-proven acute rejection episodes (BPAR) and adverse events (AE). Renal function was followed with GFRm using 51-Chromium EDTA clearance at baseline, 3 months, and 1 year. Patients were stratified according to baseline GFRm > versus <30 mL/min/1.73 m(2). The 25 patients were enrolled for MMF (n = 13) or SRL (n = 12). The median age at inclusion was 59 years (range, 25-66) and the median number of years after OLT was 4.4 (range, 1-13). Twenty-two patients were followed up for a year; MMF (n = 12) and SRL (n = 10). RESULTS: Mean GFRm for the whole cohort (n = 25) was 31+/-8 mL/min/1.73 m(2) at baseline. After 3 months the GFRm (n = 23) increased to 40+/-10 mL/min/1.73 m(2) (P = .0001) and at 1 year 42 +/- 11 mL/min/1.73 m(2) (n = 22). There was not significant difference between the MMF and the SRL study arms. The cohort (n = 8) with baseline GFRm <30 mL showed a 63% (P = .003) increased filtration after 1 year. There was no significant difference in the frequency or severity of AE between the study arms with the exception of oral ulcerations and persistent hypertriglyceridemia in the SRL group. Two deaths occurred, 1 in each study arm, both probably unrelated to the change in immunosuppression. There were no BPAR episodes. CONCLUSION: CNI discontinuation and replacement with either MMF or SRL resulted in a significant improvement in renal function even in those patients with severe CKD. The protocol was effective with no acute rejection episodes. The SRL arm showed a higher frequency of oral apthous ulcerations and hypertriglyceridemia. Future studies addressing long-term renal function after CNI discontinuation are needed.

Single or double arteries in the remnant kidney after donation: influence on the long-term outcome of the donor.

BACKGROUND: A kidney with a single artery is preferred for donation. We wondered how often the donor is left with double or triple arteries, and whether this has any implications for long-term kidney function. METHODS: The consecutive living donors from 1984 to 1988 were reevaluated for kidney function and outcome. RESULTS: In total, 154 donor nephrectomies were performed with an open anterior technique. Ninety-eight patients were left with a single artery to the remnant kidney and 56 (36%) with more than one. Six individuals were left with 3 arteries. The mean age at donation was 48 +/- 12 years and mean age at reevaluation was 68 +/- SD 12 years. In the group with a remnant single artery, the mean preoperative serum creatinine level was 87 +/- 11 micromol/L, at 6 months it was 127 +/- 20 micromol/L, and in 2007 it was 90 +/- SD 23 micromol/L. The estimated glomerular filtration rate (GFR) was 67 +/- 18 mL/min. Thirty-three percent of donors (19/58) had developed hypertension. Among the group with multiple remnant arteries, the mean preoperative serum creatinine level was 87 +/- SD 11 micromol/L, at 6 months it was 131 +/- 21 micromol/L, and in 2007 it was 100 +/- 45 micromol/L. Estimated GFR was 64 +/- 16) mL/min. Twenty-eight percent of the donors (10/36) had developed hypertension. CONCLUSIONS: One third of kidney donors were left with double or triple arteries to the remnant kidney. The 20-year follow-up showed no significant difference in the renal function between the 2 groups.

Successful combined partial auxiliary liver and kidney transplantation in highly sensitized cross-match positive recipients.

Combined liver and renal transplantations can be performed against a positive cross-match, indicating that the liver protects the kidney from the harmful HLA antibodies. This led us to the hypothesis that a partial auxiliary liver graft may have a similar protective effect when performed together with the kidney in highly sensitized patients. Seven patients, with broadly reacting HLA antibodies and positive crossmatches, were transplanted with a partial liver and a kidney from the same donor. In one of the cases a living donor was used. We performed lymphocytotoxic and flow cross-matches before and after the transplantation. Cross-matches turned negative after grafting in five of seven cases. The kidney function was excellent, without rejections, during the follow-up (24-60 months) in these patients. In two cases the cross-match remained positive after transplantation, one with a never-functioning renal graft and the other with an early graft failure, probably due to humoral rejection. A simultaneous transplantation of a partial auxiliary liver graft from the same donor, with the sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies, can be performed successfully despite a positive cross-match and may thus be a new option of treatment for highly sensitized patients waiting for a kidney transplant.

Living kidney donors developing end-stage renal disease.

The incidence of end-stage kidney failure (ESRF) was analyzed among the cohort of 1112 living kidney donors who underwent nephrectomy from 1965 through 2005. It was found that at least six persons had developed ESRF at 14 to 27 years (median = 20 years), following donation. Five of six were men. Five were parents and one, a sibling. The diagnoses were nephrosclerosis (n = 4), postrenal failure (n = 1), and renal carcinoma (n = 1). One donor, aged 45 years, underwent kidney transplantation.

Outcome of renal transplantation subsequent to liver, heart, or lung transplantation.

Renal dysfunction is a growing problem after liver, heart, or lung transplantation with the subsequent need for dialysis or renal transplantation. The aim of this study was to analyze the outcome after a subsequent kidney transplantation (secondary kidney transplantation) in liver, heart, or lung transplantation recipients. All secondary kidney transplantation patients from 1985 to 2006 were identified for the cause of kidney failure, time after initial transplantation, and current kidney function. One thousand two hundred three patient charts were reviewed including 22 (1.8%) secondary kidney transplantations: eight after lung, eight after heart, and six after liver transplantation. Renal failure was the result of perioperative renal failure (n = 3), toxic effects of cyclosporine (n = 16), a combination of cyclosporine nephrotoxicity and vascular ischemia (n = 3), or chronic renal failure due to polycystic kidney disease (n = 1). The median time after the initial organ transplantation was 114 months (range 30 to 241 months). The most recent median creatinine value was 103 micromol/L (82 to 704 micromol/L). Renal transplant rejection was noted in five patients: four in the lung transplant group, and one after heart transplantation. Three patients were deceased, one from secondary renal failure. One renal allograft was removed after renal artery thrombosis. In conclusion, there is sometimes a need for subsequent kidney transplantation after liver, heart, or lung transplantation. The outcome of renal transplantation subsequent to liver, heart, or lung transplantation is good with satisfactory renal function in this study population.

Chronic allograft nephropathy--biopsy findings and outcome.

BACKGROUND: Chronic allograft nephropathy (CAN) is a composite term for various types of damage to a kidney transplant. We wanted to analyse its components in relation to baseline biopsy findings, transplant function, and outcome. METHODS: Among renal transplantations performed from 1985 to 1997, 156 were identified where allograft biopsies had been obtained on clinical indication 6 months after transplantation or later, baseline biopsies were available in each case and the patient's original disease was known. Time after transplantation was median 2.2 years (range 0.5-13). The biopsies were reviewed and the Banff 1997 CAN score obtained. RESULTS: All but one late biopsy showed some CAN grade, 48% grade II, and 7.5% grade III. Acute tubulointerstitial rejection was seen in 9% but vascular rejection in only 3%. Arterial wall thickening was present in 66% of the late biopsies, correlated with donor age and its presence at baseline but also with time after transplantation. The Banff CAN score and serum creatinine level were both independent predictors of further graft survival, relative risk 0.35 (confidence interval 0.15-0.82, P=0.015) for CAN grade I vs III and 0.30 (0.14-0.67, P=0.003) for serum creatinine <170 vs >250 micromol/l. Presence of arterial wall thickening had no prognostic impact. CONCLUSION: The CAN grade is predictive of further graft survival independently of the serum creatinine level. Interstitial fibrosis and tubular atrophy are more prominent features of chronic graft damage than vascular rejection. Unspecific arterial wall thickening is partly dependent on baseline conditions and lacks prognostic impact in this late stage.

Low absolute glomerular filtration rate in the living kidney donor: a risk factor for graft loss.

BACKGROUND: There is no defined lower acceptable level of glomerular filtration rate (GFR) in potential living kidney donors. Considerations focus on the risk for the donor. We wanted to evaluate the outcome in the recipient in relation to the GFR of the living donor. METHODS: There were 344 living donated kidney transplantations performed January 1985 through February 1997 which were evaluated. Two thirds of the donors shared one haplotype with the recipient and 15% shared both. Of the donors 18% were above age 60. The median follow-up time (until graft loss) was 63 months. Before nephrectomy, the donors' GFR had been measured by isotope clearance. RESULTS: Twenty-six donors (7.6%) had an absolute GFR below 80 ml/min, i.e. not adjusted to 1.73 m2 body surface area (BSA). Cumulative graft survival, censored for graft loss because of death of the patient, was significantly reduced in recipients of grafts from donors with GFR <80 ml/min. A significant correlation between GFR and donor age was observed, but donor age per se was not identified as a risk factor for graft loss. In a Cox stepwise proportional hazards analysis, the relative risk for graft loss was 2.28 with a GFR below 80 ml/min (confidence interval 1.183-4.383, P=0.014) and with sharing one or both haplotypes 0.56 (0.313-0.988, P=0.046) and 0.36 (0.139-0.912, P=0.03), respectively. CONCLUSIONS: An absolute GFR below 80 ml/min in the living donor more than doubles the risk of graft loss. This fact should be considered when definitions of acceptable limits for donor GFR are discussed.

Clinical risk factors for recurrence of IgA nephropathy.

No clinical risk factors for recurrence of immunoglobulin A (IgA) nephropathy in kidney transplants have been defined. This is a single-centre retrospect analysis of recurrence in 104 first kidney transplant patients with biopsy-verified IgA nephropathy. Fifty patients had living donors. All but an identical twin were treated with cyclosporin A. The median follow-up time was 5 yr. Graft biopsies had been obtained from 35 grafts later than 6 months after transplantation, due to deteriorating graft function or gross proteinuria. Thirteen biopsies showed mesangial glomerulopathy proliferative in eleven cases with IgA deposits. Recurrence caused failure of six grafts. Eleven grafts with recurrence were from living donors (p = 0.005). No specific human leukocyte antigen (HLA) was identified as a risk factor. Known duration of original disease until end-stage renal failure was significantly shorter in patients with recurrence (median 5 yr, range 0-25 yr) compared with those without (median of 10 yr, range of 0-37 yr) (p = 0.015). Cumulative graft survival was not reduced in living versus cadaveric donor recipients.

Increasing prevalence of cardiovascular disease in kidney transplant patients with Type 1 diabetes.

Type 1 diabetes was evaluated as a risk factor in kidney transplantation with respect to cardiovascular disease and with focus on changes over time. From 1985 to 1993, 159 Type 1 diabetic patients received first kidney transplants in Göteborg. Actual 5 year-survival of diabetic patients was 75% compared to 94% for matched controls, P < 0.0001, and survival of grafts was 60% compared to 75%. In the diabetic group, high age and preexisting coronary heart disease were additional, independent risk factors. When patients were divided into three groups according to time of transplantation, survival was found to improve initially but then declined, P = 0.03. Patients in the last group were older and 39% had pre existing vascular disease. The fact that Type 1 diabetic patients now reach end-stage renal failure at a higher age and with more established vascular disease calls for careful evaluation of a larger proportion of the transplant candidates.

Morphologic high-risk factors in IgA nephropathy.

AIM: Morphologic risk factors for developing end-stage renal failure (ESRD) due to IgA nephropathy may be difficult to identify in populations where the course is benign in the vast majority. Ours is a high-risk population. METHODS: Protocols of 67 biopsies from native kidneys of kidney transplant patients with IgA nephropathy were reevaluated with respect to the prevalence of certain structural findings. Time points for onset of symptoms, biopsy procedure, and ESRD were recorded. RESULTS: Features seen with more than expected frequency were: extracapillary proliferation in 49%, cellular infiltrates in the interstitium in 89%, marked tubular atrophy in 54%, and IgA deposits in the peripheral capillary loops in 71%. With extracapillary proliferation the remaining time to ESRD was 3.5 +/- 3.2 versus 7.0 +/- 4.2 years without (p < 0.0004). With marked tubular atrophy the remaining time was 3.5 +/- 2.7 and 8.2 +/- 4.2 years without (p = 0.0002). Cellular infiltrates in the interstitium also signified shorter progression (p = 0.009). Except for the presence of IgA in the periphery, no finding by immune fluorescence was more frequent than expected or correlated with progression. CONCLUSION: Extracapillary proliferation, interstitial cellular infiltrates, marked tubular atrophy, and IgA deposits in the peripheral capillary loops indicate risk of progressive renal failure in IgA nephropathy, but other findings by immune fluorescence do not.

Focal segmental glomerulosclerosis in a kidney transplant population: hereditary and sporadic forms.

Between 1985 and 1993, 16 of 1000 kidney transplant patients in Göteborg had biopsy-verified primary focal segmental glomerulosclerosis (FSGS), and among them they received 23 transplants. Their age range was 19-67 years (median 39 years). Patients were followed for 3-10 years (median 6.5 years). Eight patients were members of seven separate families in which at least one other member had FSGS, while eight cases were sporadic. The patients with hereditary FSGS were younger at onset of symptoms than sporadic cases (median 12.5 vs 26 years, P = 0.041) but not at the time of renal failure. Only one versus five had received immunotherapy. After transplantation, recurrence of FSGS occurred in five grafts, all in sporadic cases, and two of these were lost. In conclusion, it appears that there are at least two forms of FSGS, one hereditary and one sporadic form. The hereditary form does not seem to recur after transplantation, whereas the risk in sporadic cases is very high.

Rejection rates in kidney transplant patients with and without IgA nephropathy.

BACKGROUND: Based on graft survival rates it has been claimed that patients with IgA nephropathy have a reduced risk of rejection after kidney transplantation. We wanted to evaluate this hypothesis. METHODS: Certified IgA nephropathy was the original disease in 70 of 874 consecutive kidney transplant patients (8.0%). Eighty per cent of the patients were men. Median age was 37 years, range 9-64. Fifty-three per cent had living donors and 20% of the transplantations were pre-emptive. Non-diabetic patients matched for age, sex, type of donor, and transplant number served as controls. Median follow-up time was 68 months. Duration of treatment for rejection during the first year post-transplant and graft loss due to rejection was recorded. RESULTS: The fraction of patients treated for rejection during the first year was 53% versus 54% of controls and the number of days when any antirejection treatment was given was 5.0 +/- 7.5 versus 5.5 +/- 7.4. Actual 3-year graft survival was 81% versus 80% and the number of grafts lost due to rejection was 9 versus 11. CONCLUSIONS: Rejection rates were not reduced in patients with IgA nephropathy and survival of grafts and patients not better than for matched controls.

Autosomal dominant polycystic kidney disease in a kidney transplant population.

AIM: To define specific manifestations of autosomal dominant polycystic kidney disease in kidney transplant patients. METHODS: Of 874 consecutive first renal transplant patients 1985-1993, 114 (13%) had autosomal dominant polycystic kidney disease (ADPKD). Mean age was 53 +/- 8 years, 62% were men, and 83% received cadaveric kidneys. Control patients were matched for sex, age and donor type. Median follow-up time was 63 months. One patient was lost to follow-up. Medical records before and after transplantation were reviewed. RESULTS: Survival of patients and grafts was similar in ADPKD patients and controls. Twenty-five ADPKD patients died, four of causes not seen in the controls; two aortic aneurysms, one urothelial cancer, one colon perforation. Four more ADPKD patients but no control had diverticulitis (P = 0.03), two with perforation. Cardiovascular morbidity was not increased. Eight patients had subarachnoidal haemorrhage before transplantation and two during follow-up. Nineteen patients had undergone nephrectomy before transplantation, 11 because of voluminous kidneys, five for infection, pain or bleeding, two for suspected malignancy, one for hypertension. After transplantation, seven patients underwent nephrectomy, only one related to kidney size. During the first year, need of phlebotomy occurred in 14% of patients versus 4% of controls, P = 0.02. Urinary tract infection rates were not increased. No morbidity was related to liver cysts. CONCLUSION: The specific features of kidney transplantation to patients with ADPKD were few: enlarged kidneys, relevant only before transplantation, erythrocytosis, and as rare but serious events, diverticulitis with perforation.

Systemic vasculitis in a kidney transplant population.

BACKGROUND: Systemic vasculitis as original disease might adversely influence the result of kidney transplantation. METHODS: The clinical course after 32 transplantations to 26 patients with microscopic polyangiitis, Wegener's granulomatosis, Henoch-Schonlein purpura, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, or Goodpasture's disease was evaluated. The median follow-up time was 82 months (range, 4-132 months). Frozen sera from 25 transplantations were analyzed for Goodpasture antibodies, myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA), and proteinase 3 ANCA. RESULTS: Survival of patients and grafts did not differ between patients and matched controls. Recurrent vasculitis occurred with seven grafts (four patients with microscopic polyangiitis or Wegener's granulomatosis, two patients with Henoch-Schonlein purpura, and one patient thrombotic thrombocytopenic purpura). New-onset hematuria was the initial renal symptom in five patients. Treatment with corticosteroids, cyclophosphamide, and/or plasma exchange was most often effective, but two grafts were lost. Proteinase 3 ANCA titers were increased to 12-738 U/ml before seven transplants. The patient with the lowest titer lost his graft due to recurrence, two other patients had reversible recurrence after 1 year and 5 years, two patients lost their grafts due to unknown/unrelated causes, and two patients' grafts remain without recurrence. Myeloperoxidase ANCA were increased to 22-39 U/ml before two transplants, which have been uneventful for 4 years. CONCLUSIONS: An awareness of the small but perpetual risk of recurrence facilitates early treatment that may save the transplant. Testing for hematuria and early transplant biopsies, and possibly monitoring of ANCA titers, are essential, but pretransplant ANCA titers have no predictive value in asymptomatic patients. Results of kidney transplantation in patients with vasculitis are as good as in other patients.