No impact of cross-reactive group human leucocyte antigen class I matching on long-term kidney graft survival.

UNLABELLED: The aim was to elucidate the effect of matching for the broad human leucocyte antigen (HLA)-A and -B cross-reactive groups (CREGs) of major histocompatibility complex (MHC) class I on long-term kidney graft survival. MATERIAL AND METHODS: 1304 patients transplanted at Rigshospitalet between 1968 and 1999 with a cadaver kidney and followed until 2000. The definition of CREGs based on amino acid residues was according to United Network for Organ Sharing (UNOS) (1996). Graft-survival analyses (Kaplan Meier) were performed for all cases and for cases censored for death with functioning grafts. RESULTS: Univariate analysis showed no effect of any specific donor or recipient CREG on graft survival. Contrary to some reports in the literature, the absolute and relative number of CREG shares and of CREG mismatches had no effect on graft survival even when censored for graft loss because of death. However, graft survival was dependent on DR shares (P < 0.05), indicating that matching for MHC class II seems to be more important than that for the broad MHC class I phenotype represented by CREG.

Pyelonephritis and interstitial nephritis--clinical-pathological correlations.

AIMS: The relation between histological and clinical parameters were studied in 54 consecutive patients with acute interstitial nephritis or pyelonephritis without primary glomerular disorders, in all of whom percutaneous renal core biopsy had been performed. PATIENTS AND METHODS: Based on clinical criteria and without detailed knowledge of the appearance of the biopsy, the material was divided into 4 main groups: patients with septic and/or tubulotoxic conditions, hypersensitivity reactions (eosinophilic nephritis), ascending infections and other specified conditions. RESULTS: The overall correlation between the histological and the clinical diagnoses was good, but there were large overlaps between the histological findings in 3 of the groups, making classification of individual cases difficult. The histological and paraclinical findings were poorly correlated. Histologically, ascending infections were characterized by the presence of leukocyte casts and an increased number of neutrophilic granulocytes. CONCLUSION: The material justifies the present rough classification of the conditions mentioned above. By kidney biopsy, the interstitial conditions can be separated from glomerular and other conditions, but the biopsy offers little information about the clinical severity or the prognosis.

Kidney transplantation activity and outcome in Denmark 1990-1999.

1. During the period 1990-1999, 1,715 renal transplants were performed in Denmark, corresponding to 31.8 per million population per year. Seventy-five per cent were cadaver donor transplants; in 25%, a living donor kidney was used. 2. Living donors of 437 kidneys were mainly parents (54%) and siblings (36%). In 20 transplants, a kidney from a living-unrelated donor was used. 3. The overall actuarial patient survival rates at one and 5 years were 91.0% and 78.2%, respectively. The major causes of recipient death were cardiovascular disease and infection. 4. The overall actuarial graft survival rates at one and 5 years were 81.4% and 62.0%, respectively. The major single causes of graft loss were rejection (41%) and recipient death (32%). Graft survival has improved during the decade.

The effect of acute rejection on long-term renal graft survival is mainly related to initial renal damage.

It has been suggested that poor long-term prognosis of acute rejection is due to hyperfiltration-mediated injury secondary to the initial renal damage, rather than to ongoing immunological mechanisms. A total of 953 renal transplant recipients was reviewed to examine the effect of acute rejection episodes on graft function and survival; 40% had no rejections, 45% one, 12% two and 3% three. Rejection episodes adversely affected short- and long-term prognosis (5-year survival for no rejections, 62%; one, 34%; two, 26%; three, 19%, P < 0.001) and creatinine clearance at one year (cl 1) (none, 56.7 ml/ min; one, 51.1; two, 52.9; three, 35.2, P < 0.01). This was mainly due to increased graft loss, but patient survival was also reduced (5-year survival for no rejections, 77%; one, 76%; two, 63%; three, 53%, P < 0.05). There was no overall effect of rejection number, independently of cl 1. However, subgroup analysis showed a detrimental effect of rejection number on grafts with high residual function, i.e. cl 1 > 60 ml/min (5-year graft survival none and one, 87%; two and three, 71%, P < 0.01). Late initial rejection episodes adversely affected prognosis (5-year survival 1-7 days, 34%; 8-60, 31%; 60-300, 21%, P < 0.05) and residual graft function (cl 1 1-7 days, 56.2 ml/min; 8-60, 48.7; 60-300, 44.6, P < 0.01). In conclusion, the poor long-term prognostic effect of rejection episodes is mainly, but not entirely, related to initial graft destruction. Late (> 2 months after transplantation) initial rejection is an important independent risk factor for graft loss.

Castleman's disease with renal infiltration by polyclonal plasma cells.

A 52-year-old man was admitted to hospital because of declining renal function. Some months previously, biopsy from a mediastinal lymph node had shown Castleman's disease (angiofollicular lymph node hyperplasia). By now, a renal biopsy showed massive interstitial infiltration of predominantly plasma cells without significant atypia. On immunostaining, the plasma cells showed cytoplasmic reaction for IgG and kappa and lambda light chains, which had also been the case with the mediastinal lymph node. These findings were interpreted as interstitial renal involvement of Castleman's disease. The patient was treated with prednisone, upon which the renal function was stabilized, but not improved. The attention is drawn to Castleman's disease as a possible, although rare, cause of renal interstitial cellular infiltration.

Immunohistochemical study of actin binding protein (p55) in the human kidney.

BACKGROUND: In clinical transplantation, "passenger" dendritic cells (DCs) in the allograft have been thought to induce allograft rejection. However, the presence of DCs in the normal human kidney is controversial. Most reports have relied on the examination of MHC class I and II antigen expression in combination with DC morphology for identification of DCs. METHODS: The distribution of the p55 antigen (fascin), which is selectively expressed by human blood and lymphoid DCs, was investigated by immunohistochemistry. RESULTS: Our study demonstrates that p55-positive DCs are absent from the normal human kidney and CD1a- and S100-positive cells are absent or very rare. Furthermore, HLA-DR and factor VIII-related antigen show almost complete colocalization in capillaries. In contrast, all 16 kidney biopsies from patients with inflammatory processes demonstrated p55-positive DCs in the cellular infiltrates. CONCLUSIONS: These results suggest that DCs are not present or are very rare in normal renal tissues but may migrate into the renal interstitium with inflammatory changes.

Hyperfiltration, creatinine clearance and chronic graft loss.

Chronic graft loss (CGL) may be caused by immunological- or hyperfiltration-mediated tissue destruction. If the hyperfiltration theory is correct, grafts from female donors given to heavy recipients, and having a relatively poor initial function, should suffer an accelerated rate of loss of function. 590 renal transplantations surviving more than 1 yr, including 171 cases of (CGL), were reviewed to identify causes of CGL. No overall influence of recipient or donor sex was found, but female donation resulted in lower acute graft loss and higher CGL. Warm ischemia affected CGL marginally, but cold ischemia < 12 h (excluding living donors) reduced CGL (35 vs. 53% at 10 yr, p < 0.05) and delayed function increased CGL (38% vs. 56% p < 0.001). Patients with a high urea production had high CGL (43% vs. 77%, p < 0.02). No overall effect of recipient weight was found; however 7 patients weighing > 90 kg all had CGL within 10 yr. Creatinine clearance was increasingly correlated to recipient weight (r = 0.23 at 1 yr, 0.38 at 10 yr, p < 0.001). For all years, change in creatinine clearance correlated with change in weight (p < 0.001). The most important factor predicting CGL was creatinine clearance, (> 80 ml/min: 6% at 10 yr; 20-40 ml/min 53%). However, at any level of creatinine clearance, patients with late CGL had a slower loss of renal function. Rate of change of renal function was proportional to creatinine clearance, but only for grafts surviving > 6 yr. Creatinine clearance rose between 3 mths and 2 yr; this rise indicated a good prognosis, was related to recipient weight and weight increase, and was reduced in older donors and cyclosporine treated patients. For patients with low clearance (< 60 ml/min), the increased CGL seen in patients with previous rejection episodes could be explained by their consequent lower clearance, but above this level, rejection episodes had an independent deleterious effect. These findings are compatible with hyperfiltration being the major cause of CGL after 6 yr. Before this immunological factors dominate. Good quality grafts respond to the increased protein load of heavy recipients with an increased GFR. Thus at any time, graft GFR is a function of protein-induced hyperfiltration, immunological graft destruction and hyperfiltration-mediated damage. Hyperfiltration-mediated renal damage is not a problem if the creatinine clearance is greater than 60 ml/min.

Interaction between proximal tubular cells and allogenic leukocytes mediated by interleukin-1 and prostaglandin.

The present study investigates the interaction between proximal tubular cells (TC) and peripheral blood mononuclear cells (PBMC) with respect to interleukin-1 (Il-1) and prostaglandin E2 (PGE2) in co-culture experiments. Stimulator cells were proliferating human TC propagated in culture and characterized by expression of ICAM-1 and MHC-class II in response to cytokines. The presence of TC reduced spontaneous growth of PBMC by 42%, with a concomittant 50% reduction of Il-1 release and a 6-fold increase of PGE2 release in the growth medium. The growth reduction was partly counteracted by addition of II-1 and indomethacin. Addition of II-1 stimulated the PGE2 release from PBMC and TC by about 75% and 500%, respectively. Growth of TC cultured alone was inhibited by II-1 in a dose-dependent manner, with maximum effect at 10 U/ml, whereas PGE2 showed no effect. These results suggest that TC have the capacity to interact with PBMC, and this potentially tissue-protective mechanism induced by TC may have clinical implications.

Staphylococcus aureus carriage and infections among patients in four haemo- and peritoneal-dialysis centres in Denmark. The Danish Study Group of Peritonitis in Dialysis (DASPID).

A three-month prospective surveillance study was undertaken in four dialysis centres to establish the prevalence of Staphylococcus aureus carriage in a Danish population of patients on haemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). General data such as sex, age, diagnosis, number of months in dialysis, hospital and ward were registered on a precoded form. Standardized nose and four skin swabs (axillae, groins, perineum) were performed on the first day of the survey. After one and two months, nose swabs were collected. Infections were registered and cultures were sent for phage-typing together with the S. aureus strains isolated from the swabs; 59.5% of HD patients and 51.2% of CAPD patients carried S. aureus. Permanent carriage was most frequent (P < 0.00009), primarily in the nose (44.0 and 34.9%, respectively in HD and CAPD). Skin carriage alone was rare (2.4 and 4.7%). Approximately one third (36.6 and 40.7%) of infections were caused by S. aureus. Although diabetics were not significantly more frequent carriers (60.5%) than non-diabetics (55.0%), the incidence of infection was much higher (26.3% vs. 10.3%, P = 0.004). In CAPD, peritonitis and tunnel/exit-site infections predominated (81.4%), often caused by S. aureus (34.8%). More than two thirds of the infections in HD patients were related to intravascular catheterization. The most serious infection was septicaemia, in all cases due to S. aureus. S aureus infections occurred significantly more frequently among carriers (P = 0.005), and more than half the patients were infected by the same or possibly the same strain as they carried in the nose or on skin. Different regimens for the elimination of S. aureus carriage in dialysis patients are discussed. A policy for risk assessment of patients should be developed, and the elimination of S. aureus carriage before dialysis should be encouraged. Controlled trials comparing the cost-effectiveness of recommended regimens to eliminate carriage in HD/CAPD patients are needed. Nose swabs are reliable indicators of carriage in dialysis patients.

[Glomerular tip lesions--a newly described glomerular change]. / Glomerulaer tip lesion--en nyerkendt glomerulaer forandring.

Glomerular tip lesion is a newly described histopathological lesion characterized by a focal and segmental widening of the mesangial matrix without hypercellularity together with capillary dilatation, hyaline exudation on the inside of capillary walls and occurrence of vacuolized cells, localized to the peripheral segments of the glomerular tuft. Clinically, these patients have a pronounced nephrotic syndrome with slightly reduced renal function, but terminal renal failure is seldom seen, even after many years of disorder. Two characteristic case histories are presented. The classification of this lesion among the glomerular disorders is at present uncertain. It may represent a transitional form between minor lesion nephritis and focal segmental sclerosis, a separate disorder, or a functional lesion associated with high proteinuria.

Circadian variation of blood pressure in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

The circadian pattern of blood pressure variation was investigated in 10 patients with advanced chronic renal failure on continuous ambulatory peritoneal dialysis (CAPD) and in an age-matched group of controls without renal disease with similar office blood pressure level. Monitoring was done using a non-invasive ambulatory blood pressure recorder. Average 24-h blood pressure was significantly higher in the group of CAPD patients than in the group of healthy controls, i.e. 141 +/- 22/82 +/- 8 mmHg (systolic and diastolic blood pressure +/- SD) vs. 126 +/- 18/80 +/- 7, p < 0.1. This was a result of abnormal 24-h blood pressure profiles among CAPD patients. In the group of controls these profiles were in accordance with the established normal pattern, whereas nocturnal blood pressure reductions were significantly less pronounced in the patient group. The reduction +/- SD in the mean arterial blood pressure was 2 +/- 6 mmHg in patients versus 10 +/- 5 mmHg in controls, p < 0.01. The mean arterial blood pressure values during daytime (0800-2000 h) exceeded the night time values (2000-0800 h) in all healthy controls, whereas four of 10 patients had higher blood pressure values during the night time. In patients with chronic renal failure undergoing CAPD, an otherwise unnoticed 24-h hypertension and nocturnal blood pressure elevation can be discovered by use of 24-h blood pressure monitoring and this may indicate a need of earlier start of antihypertensive treatment in CAPD patients with borderline daytime hypertension.

Comparison of straight and curled Tenckhoff peritoneal dialysis catheters implanted by percutaneous technique: a prospective randomized study.

OBJECTIVE: To examine the impact of peritoneal dialysis catheter configuration, curled or straight catheter, on catheter survival and mechanical and infectious complications. DESIGN: Prospective randomized trial. SETTING: Department of Nephrology of a single university hospital. PATIENTS: Seventy-two consecutive patients initiating peritoneal dialysis were randomized to receive either a single cuff straight catheter or a single cuff curled catheter, implanted by percutaneous technique. RESULTS: Significantly higher (p < 0.01) survival rate of the curled as compared to the straight catheter. The difference in catheter survival was due to a significantly higher (p < 0.01) incidence of drainage failure associated with catheter tip migration of the straight catheter than of the curled catheter. No difference in infectious complication between the two types of catheters was seen. Catheter survival at 12 months was 77% for the curled catheter and 36% for the straight catheter. CONCLUSION: This study demonstrates superiority of the curled Tenckhoff peritoneal dialysis catheter survival as compared to the straight catheter. This difference in catheter survival is due to the higher displacement rate of the straight catheter.

Lean body mass by Dual Energy X-ray Absorptiometry (DEXA) and by urine and dialysate creatinine recovery in CAPD and pre-dialysis patients compared to normal subjects.

The urinary creatinine excretion rate is a function of the muscle mass which, in normal subjects, is shown to be correlated with lean body mass. Dual Energy X-ray Absorptiometry (DEXA) has been shown to correlate well with other methods for the measurement of body composition. The purpose of the present study was to compare estimates of lean body mass (LBM) by DEXA scan with urine and dialysate creatinine recovery in uremic patients and in normal subjects. We included 63 normal subjects with a creatinine clearance of 60-120 mL/min, 30 uremic predialysis patients with creatinine clearance below 30 mL/min, and 20 continuous ambulatory peritoneal dialysis (CAPD) patients. LBM was measured by DEXA scan on the same day as urine collection and was estimated from creatinine recovery with and without correction for extrarenal creatinine clearance. Results from the normal subjects showed no difference in estimates of LBM by the different methods but, in predialysis and CAPD patients, a significant difference between methods of estimating LBM was found, even when correction for extrarenal clearance in uremic patients was performed. In normal subjects: DEXA 43.6 kg versus creatinine excretion 43.2 kg (NS). In predialysis patients: DEXA 47.8 kg versus 37.6 kg (p < 0.001) corrected 44.8 kg (p < 0.05). In CAPD patients: DEXA 47.2 kg versus 32 kg (p < 0.001) corrected 42.6 kg (p < 0.05). In conclusion, the urine and dialysate creatinine excretion is an inaccurate estimate of LBM, but reflects the muscle mass and, in that respect, is an important tool in the nutritional evaluation of uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid hormone dependent T cell proliferation in uremic rats.

Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA was normalized. Rat PTH 1-84 stimulated in vitro the PHA-induced proliferation of T cells in a dose dependent manner. This effect was significant in CRF rat lymphocytes, but not in lymphocytes obtained from normal rats. Based upon the present results it is suggested that the secondary hyperparathyroidism in chronic uremia is responsible for the enhanced proliferative response to PHA of T cells from CRF rats.

Acute effects of FK506 and cyclosporine A on cultured human proximal tubular cells.

The effects were studied of FK506 and cyclosporine A on human proximal tubular cells. An in vitro assay was used with cultured renal cells which displayed characteristics of proximal tubular cells. Cell growth was measured by [3H]thymidine uptake. FK506 inhibited cell growth by about 50% at 1 micrograms/ml but cells were not killed as shown by the dye exclusion test. The growth rate of cells recovered to control levels after removal of FK506 from the cultures. FK506 and cyclosporine A showed an additive effect on tubular cell growth reduction. This effect was similar at equivalent doses of FK506 and cyclosporine A, whereas in cultures of leukocytes, the half maximal response to mitogen was obtained at 0.01 micrograms/ml FK506 and 0.5 micrograms/ml cyclosporine A, respectively. Immunocytochemistry demonstrated that FK506 reduced the expression of interferon-gamma induced major histocompatibility complex (MHC) class I on the proximal tubular cells, but had no effect on the expression of the MHC class II antigens or the intercellular adhesion molecule (ICAM-1) on the cultured cells.