Failure of dialysis access: revise or replace?

Providing adequate long-term dialysis access has become increasingly difficult. In order to evaluate the operative factors associated with early failure of dialysis access, 2337 operations performed in 1124 patients over an 8-year period were retrospectively reviewed. Evaluation of 1306 procedures that eventually failed and required operative revision or repair provided the basis for this study. Access failure occurred in 459 (41%) of the 1124 patients. An average of 2.8 episodes of failure (range 1-13) were observed among this group of patients, occurring after an average of 230 +/- 9 days (mean +/- ++standard error) postoperatively, with the longest interval to failure being 2529 days. The time-to-failure for revision of a preexistent arteriovenous fistula or prosthetic graft (140 +/- 9 days, n = 449) was significantly (P < 0.0001 ANOVA) shorter than for creation of an arteriovenous fistula (272 +/- 21 days, n = 336) or prosthetic graft (299 +/- 19 days, n = 372) at a new site. Procedures performed in octogenarians tended to fail earlier (178 days). Dialysis access failure tends to recur in patients with a history of previous access problems. The time-to-failure was similar for new prosthetic grafts and arteriovenous fistulas, but twice as long compared to revision of a previous access site.

New patterns of transplant nephrectomy in the cyclosporine era.

Several significant advances in transplantation during the last decade, among them the introduction of cyclosporine, have greatly altered the management of allograft recipients. To determine the frequency and pattern of transplant nephrectomy (TN) since cyclosporine was introduced in 1984, we reviewed our results from 1968 through 1990. During the 23 year period, 766 renal transplants were performed; 280 before 1984, when cyclosporine was first introduced into routine care and 486 after that time. Of the 280 recipients undergoing transplantation before 1984, 70 underwent TN, whereas only 61 of the 486 recipients in the cyclosporine period have undergone TN (p < 0.01). Comparing the demographics of those who had TN before 1984 with those who had TN in the cyclosporine era shows similarities: the mean age at TN (32 versus 32 years), percent male (66 versus 61), percent black (51 versus 61), percent of TN operations within six months of graft insertion (80 versus 70) and percent perioperative complications (nine versus 11). During the precyclosporine era, TN was performed more frequently in patients who received allografts from cadavers versus living related donors (30 versus 8 percent, p < 0.05), but this difference was eliminated after 1983 (11 versus 13 percent, p = NS). TN was performed more frequently after secondary versus primary transplants in the early (36 versus 23 percent) and later (23 versus 11 percent) time periods (p < 0.05 only for the later time period). It is also noteworthy that the rate of TN decreased significantly for primary and secondary transplants in the later time period. For low risk white patients and higher risk black patients the rate of TN decreased in an identical manner. We conclude that since the introduction of cyclosporine, TN is performed less frequently, the frequency of TN in lower risk (primary white) and higher risk (secondary, black, cadaveric) groups has decreased and TN has been and remains a safe procedure.

Renal transplantation from living related donor after excision of angiomyolipoma of the donor kidney.

A 44-year-old woman with end stage renal disease underwent living related renal transplantation after planned partial nephrectomy of the donor kidney for angiomyolipoma.

Ischemia-reperfusion injury: biochemical alterations in peroxisomes of rat kidney.

Exogenously supplied catalase, a peroxisomal enzyme, has been found to be of therapeutic value in ischemic injury. Therefore, we examined the effect of ischemic-reperfusion injury on the structure and function of kidney peroxisomes. Ischemic injury changed the density of peroxisomes from 1.21 g/cm3 (peak I) to a lighter density of 1.14 g/cm3 (peak II). The number of peroxisomes moving from the normal density population (peak I) to a lower density population (peak II) increased with an increase in ischemic injury. Latency experiments indicated both populations of peroxisomes to be of intact peroxisomes. Immunoblot analysis with antibodies against peroxisomal matrix and membrane proteins demonstrated that after 90 min of ischemia a significant number of matrix proteins were lost in the peak II population, suggesting that functions of these peroxisomes may be severally affected. Reperfusion following ischemic injury resulted in loss of peroxisomal matrix proteins in both peaks I and II, suggesting that peroxisomal functions may be drastically compromised. This change in peroxisomal functions is reflected by a significant decrease in peroxisomal catalase activity (35%) and beta-oxidation of lignoceric acid (43%) observed following 90 min of ischemia. The decrease in catalase activity was more pronounced in reperfused kidneys even after a shorter term of ischemic injury. Reperfusion restored the normal peroxisomal beta-oxidation in kidneys exposed up to 60 min of ischemia. However, 90 min of ischemia was irreversible as there was a further decrease in beta-oxidation upon reperfusion. The decrease in catalase activity during ischemia alone was due to the formation of an inactive complex, whereas during reperfusion, following 90 min of ischemia, inactivation and proteolysis or decreased synthesis of catalase contributed equally toward the injury. The observed changes in the structure and function of peroxisomes as a result of ischemic-reperfusion injury and the ubiquitous distribution of peroxisomes underlines the importance of this organelle in the pathophysiology of vascular injury in general.

Mitochondrial membrane fluidity changes in renal ischemia.

The fluorescence polarization technique with 1,6-Diphenyl-1,3,5-hexatriene as a probe, was used to determine the lipid rotational mobility (LRM) measured by fluorescence anisotropy of isolated whole mitochondria of the rat kidney following normothermic ischemia of 30, 45, 60 and 90 minutes and upon reperfusion for 24 hours. The LRM of mitochondrial membrane lipids of the ischemic kidney decreased steadily with increasing ischemic times (0.1590 vs. 0.1705, 0.01 less than P less than 0.001 at 60 minutes). Following 24 hours reflow, there were no significant differences in the LRM of mitochondria between ischemic and control groups up to 45 minutes of ischemia, (0.1688 vs. 0.1705, 0.5 less than P less than 0.6). However, when kidney was subjected to ischemic periods longer than 60 minutes, the decreased LRM remained fixed even after reperfusion (0.1783 vs. 0.1738, 0.5 less than P less than 0.6). This suggests that 60 minutes of ischemia probably produces irreversible damage to the mitochondrial membrane whereas lesser degrees of ischemic injury is reversible upon reperfusion.

Effect of ischemia and 24 hour reperfusion on ATP synthesis in the rat kidney.

The ability of renal tissue to synthesize ATP was examined in adult Sprague Dawley Rats immediately following normothermic ischemia of 30, 45, 60 and 90 minutes and upon reperfusion for 24 hours. Following ischemia the rate of ATP synthesis decreased progressively. It was 64.5% of the control at 45 minutes and 10.4% after 90 minutes of ischemia. Reperfusion of the ischemic kidneys for 24 hours restored ATP biosynthesis to control, nonischemic levels in kidneys subjected to ischemia up to 45 minutes (101.8 +/- 13.9% vs 64.5 +/- 2.5% p less than 0.02). However, after 60 minutes of ischemia, reperfusion had no effect (59.3 +/- 4.4% vs 51.7 +/- 7.5%) and reperfusion following 90 minutes of ischemia was associated with decrease ATP synthesis (10.4 +/- 2.2% vs 3.3 +/- 0.9% p less than .001). We conclude that mitochondrial function is restored by reperfusion when normothermic ischemic interval is 45 minutes or less. However, ischemic intervals longer than 45 minutes produce non-reversible impairment of ATP synthesis and the marked reduction following 90 minutes of ischemia signifies possible transition to a non-viable state.

Necrotizing fasciitis in a renal transplant patient.

We have described a 28-year-old diabetic woman who had necrotizing fasciitis of the perineum three years after receiving a living related renal transplant. The diagnosis of necrotizing fasciitis was made early and she was referred to a tertiary care center where she received radical perineal debridement and aggressive medical and surgical follow-up. Necrotizing fasciitis in a transplant patient is rare; review of the literature shows few cases and no survivors. Our patient has returned to a normal life despite continuation of all immunosuppressive therapy throughout the entire hospital course. In addition, she had a good cosmetic result despite the large necrotic perineal infection. Her survival can be attributed to early diagnosis and referral, immediate and extensive debridement, and aggressive protein replacement.

Fatty acid metabolism in renal ischemia.

The increase in free fatty acids in the ischemic tissue is a consistent observation and these free fatty acids are considered to play a role in the cellular toxicity. To elucidate the cause of higher levels of free fatty acids in ischemic tissue, we examined the catabolism of fatty acids. The beta-oxidation of lignoceric (24:0), palmitic (16:0) and octanoic (8:0) acids and the peroxidation of fatty acids were measured at different times of renal ischemia in whole kidney homogenate. The enzymatic activities for the oxidation of fatty acids decreased with the increase in ischemia time. However, the lipid peroxide levels increased 2.5-fold of control with ischemic injury. Sixty min of ischemia reduced the rate of oxidation of octanoic, palmitic and lignoceric acids by 57, 59 and 69%, respectively. Almost similar loss of fatty acid oxidation activity was observed in the peroxisomes and mitochondria. These data suggest that loss of mitochondrial and peroxisomal fatty acid beta-oxidation enzyme activities from ischemic injury may be one of the factors responsible for the higher levels of free fatty acids.

Prevention of acute tubular necrosis after transplantation: effect of pretransplantation volume expansion.

We reviewed our experience with 100 consecutive cadaveric transplants of kidneys from satisfactory donors with respect to immediate function after transplantation. The management was the same in all patients except that 66 of them received 1,000 ml of 0.9 N saline IV preoperatively. The overall incidence of acute tubular necrosis (ATN) was 23.2%, but the incidence of ATN in the group of patients who received saline was 7.6%, as compared to 53% in those that did not (P less than .001). There was no other significant difference between the two groups. We conclude that when cadaver kidneys are harvested and preserved under satisfactory conditions, preoperative volume expansion markedly lowers the incidence of posttransplantation ATN, suggesting that the recipient volume status is an important consideration.

Renal transplantation in Alport's syndrome.

Nineteen patients (3 women and 16 men) with Alport's Syndrome and endstage renal failure received 23 allograft kidneys at two medical centers between 1972 and 1983. Ten patients had pretransplant splenectomies, and four patients had pretransplant thoracic duct drainage. After a mean follow-up time of 49 months, analysis revealed total allograft survival was 65 per cent at 1 year, 50 per cent at 2 years, and 57 per cent at 5 years. Pretransplant splenectomy resulted in 60 per cent allograft survival at 24 months mean follow-up. Pretransplant thoracic duct drainage resulted in 100 per cent allograft survival at 15.6 months mean follow-up. The overall allograft survival was greatest for three and four antigen-matched kidneys and for living related donor kidneys. Data indicated that 50 per cent of all allografts in men were functional at 50.8 months mean follow-up. All allografts in women were functional at 48.3 months mean follow-up. Three of four patients who expired had pretransplant splenectomies. From this study, the authors conclude that renal transplantation is the preferred method of treatment for patients with Alport's Syndrome.

Reversal of acute renal failure using hemodilution with hydroxyethyl starch.

Acute renal failure (ARF) was induced in two groups of unilaterally nephrectomized dogs by occluding the renal artery, vein, and ureter of the remaining kidney for 2 hours. The control group (Group I), had no therapy; in the experimental group (Group II), isovolemic hemodilution was carried out using 6% hydroxy ethyl starch (HES) as diluent. The hematocrit in the experimental animals was lowered from 41.62 +/- 3.6% to 23.75 +/- 5.2% after renal occlusion. The mean arterial pressure and the mean pulmonary arterial pressure were unchanged in either group. Cardiac output increased following hemodilution from 1.66 +/- 0.35 to 2.70 +/- 0.50 L/min while it remained unchanged in Group I. Control animals developed ARF characterized by progressive rise in serum creatinine concentration and death. Only 1/7 Group I animals was alive on day 7 compared to 7/7 of Group II (p less than 0.01). ARF that developed initially in Group II began to resolve after day 4. There was a progressive and significant fall in serum creatinine concentration from 6.48 +/- 0.67 mg/dl on day 4 to 4.08 +/- 0.83 mg/dl on day 7 (p less than 0.001). Immediate isovolemic hemodilution with HES can reverse ARF induced by ischemia.

Antigen-coated immunoadsorbents utilized for in vivo depletion of antibodies and lymphocytes with specificity for the antigen.

Hyperacute rejection of xenografts is thought to be triggered by humoral antibodies. It is known that natural antibodies against dog blood cells have been identified in sheep serum. Dog kidney antigen immunoadsorbent columns were placed in the extracorporeal lymph circuit of two sheep. In vivo studies have shown that these immunoadsorbent columns were effective in depleting the thoracic duct lymph of all antibodies with specificity for the dog kidney antigen. However, these columns were not effective in depleting the thoracic duct lymphocytes bearing surface receptors for the dog kidney antigen. When in vitro studies were carried out, the immunoadsorbent columns were effective in the depletion of both lymphocytes and antibody for the dog kidney antigen. Thus, since a humoral antibody response is thought to be responsible for the hyperacute rejection seen in xenografts, it is possible that these columns might be effective in prolonging xenograft survival.

Characterization of the preformed antibodies involved in the xenograft reaction.

The dog-to-sheep renal xenograft model was utilized to isolate the antibodies that participate in xenograft hyperacute rejection. These sheep antibodies, which were isolated from the rejected dog kidney, agglutinated and killed only dog blood and kidney cells whereas the whole sheep serum reacted with both dog and rabbit cells. The purified antibody was also utilized to obtain in pure form the antigens involved in the hyperacute rejection. When this antigen was tested for its ability to bind the serum of various species, this particular antigen was highly specific for sheep serum and would not react with rabbit, horse, calf, or mouse sera.

Dialysis enhances renal epithelial proliferations.

Study of 115 kidneys from 60 patients with chronic renal failure maintained by dialysis for two months to five years revealed an unexpected number and variety of epithelial proliferative processes, several types of which are hitherto unreported. Proliferative activity was defined either by the presence of epithelial structures in ectopic situations, continuity with existing structures being demonstrable by serial sections, or by mitotic figures, or by both. The tendency for renal carcinoma development may relate to these dialysis-related epithelial proliferations originating in both glomerular and tubular epithelia. Enhanced renal epithelial proliferative capacity in dialysis may be employable in the experimental study of renal regeneration and in the therapy of patients with preterminal renal disease.