Variations in living donor graft rates by dialysis clinic: effect on outcome and cost of chronic renal failure therapy.

OBJECT: Examination of nephrology practice variations in living donor renal grafts to determine their influence on organ supply, quality, and cost of chronic renal failure therapy. MATERIALS: Saskatchewan chronic dialysis, cadaveric, and living donor renal grafts in 1983-1994 inclusive. RESULTS: Saskatchewan has three dialysis (I, II, III) and one transplant clinic. In the period the renal graft incidences/million population by these dialysis clinics by organ source were; Cadaveric: 23.1, 23.2, 21.1 (p = ns). Living: 5.4, 21.7, 8.3 (I or III vs II p < 0.000, I vs III p < 0.061). Total: 28.7, 44.7, 29.4. Living donor series A is 79 grafts in patients under age 60 with primary renal disease. Series B is 20 grafts in patients with secondary renal disease or over age 59. Series A ten-year actuarial patient survival is 92% and B 44%. Series A ten-year actuarial graft survival (including regrafts) is 77% and B 39%. Rehabilitation rate in patients with functioning grafts is 88.5%. Province-wide extension of the Clinic II living-donor graft rate in 1983-1994 would have produced 160 more renal grafts or 59% of those receiving chronic dialysis in 1994. The annual maintenance for a graft with the initial grafting cost taken over five years was $10,825 and the dialysis cost $40,100. CONCLUSIONS: (1) nephrology practice variations caused a 2.5-4.0-fold difference in living donor renal graft rates, indicating patient education by the attending nephrologist influences the living donor transplantation rate, (2) with such education the combined living donor and the cadaveric organ supply virtually meets graft demand, (3) living donor renal grafts yield a better quantity and quality of life and better cost control than dialysis with their annual cost being one-quarter that for dialysis.

Protein malnutrition and decreased protein turnover in chronic renal allograft failure.

OBJECT: To define the longitudinal relationship of declining renal function to protein consumption and turnover in the failing renal allograft model of chronic renal failure. METHOD: The study group is our first eight consecutive cadaveric renal graft recipients who after attaining a normal creatinine clearance, then developed chronic renal failure. We analysed their urea and creatinine clearances (Cur, Ccr), serum urea (SU), urinary urea and creatinine (Ur, Ucr), serum albumin (SA), urinary protein (Upr), body weight (BW), and steroid dose. Steady state Uur is also dietary protein intake (DPI) and protein catabolic rate (PCR). Ucr measures body protein mass. Ucr/Uur measures the ratio of body protein mass to urea excretion. Mean follow-up 4.7 years, range 1.5-8.7 years. RESULTS: Mean changes: (1) Body weight (BW) rose from 56 to 65 and then fell to 61 kgms. (2) Cur fell 65 to 5 and Ccr 92 to 12 ml/min/70 kg. (3) Uur fell from 369 to 107 and Ucr from 16.8 to 9.5 mmols/day/70 kg. (4) Uur/Ucr indexed at 1:1 fell to 0.49. (5) SU rose from 8.8 to 34.9 mmol/1; SA fell from 36.1 to 31.0 gms/1; Upr rose from 1.4 to 2.3 gms/day. (6) Prednisone rose from 26 to 66 and then fell to 33 mgms/day. Correlations: (1) Cur and Uur(r = 0.99, p < 0.001). (2) Ccr and Uur (r = 0.99, p < 0.001). (3) Cur and Uur/Ucr (r = 0.88, p < 0.01) with a decelerating breakpoint at Cur 18 and Ccr 32 ml/min/70 kg (p < 0.01). (4) SU and Uur negatively (r = 0.90, p < 0.01. (5) Cur and SA albumin (r = 0.82, p < 0.05). (6) Cur and prednisone, Upr and SA do not correlate. CONCLUSIONS: In this model of chronic renal failure: (1) Renal function controls protein intake. (2) Body protein mass is relatively well preserved despite the decreased protein intake implying a decrease in the protein turnover rate and a consequent increase in body protein average age. (3) Protein malnutrition, protein ageing, and decreased protein turnover are likely pathophysiological reactions to chronic renal failure and may be part of the pathogenesis of chronic uremia.

Improved urea clearance raises the BUN in continuous peritoneal dialysis.

Cross-sectional studies in steady state dialysed chronic end-stage renal failure patients show urea clearance (Kt/V) and total urea excretion (protein catabolic rate) correlate positively. However, urea clearance is total urea excretion divided by BUN. Thus urea clearance and BUN relate reciprocally, and so their mathematical product (total urea excretion) is independent of clearance. As such clearance cannot also be a positive correlate of total excretion as demanded by the cross-sectional studies. Furthermore the clearance formula dictates that the positive urea clearance and total urea excretion correlation found in the cross-sectional studies can only occur if the increased urea clearance fails to reciprocally lower the BUN. Thus the relations of urea clearance, urea excretion, and BUN requires further definition. To so define we examine dialysis urea excretion, dialysis urea clearance, BUN, and serum albumin in 13 stabilized chronic uremics with minimal native renal function who are treated by continuous ambulatory peritoneal dialysis (CAPD). Urea clearance and BUN correlate positively (r = 0.62, p < 0.05) and both also correlate positively with dialytic urea excretion and (urea clearance r = 0.912, p < 0.001, BUN r = 0.88, p < 0.001). In addition dialytic urea excretion and serum albumin indexed to body size correlate positively (p < 0.05). Thus in the steady state urea clearance associates with both an increase in BUN and urea output. However the law of conservation of mass makes urea output is a function of protein intake. Thus increased clearance cannot directly increase such output, and so increased clearance must first increase intake but in doing so it increases the retention of the byproducts of enhanced intake, BUN and other protein metabolites, so leading to a paradox, the more removed, the more remains. These observations taken together suggest that in chronic uremia treated by continuous dialysis, elevation of the BUN may be a marker for an adequate restoration of protein metabolism if inadequate dialysis is excluded.

HLA-identity--long-term renal graft survival, acute vascular, chronic vascular, and acute interstitial rejection.

The object is analysis of the impact of acute and chronic rejection on long-term function in HLA-identical renal transplants performed from 1967 to 1995 by the Saskatchewan Renal Transplant Unit. Forty-eight grafts in 46 patients were studied, of which 39 were first and nine second grafts. Forty-two were for primary and six for secondary renal disease. Thirty-five received azathioprine/prednisone prophylaxis, and 13 received cyclosporine/prednisone with/without azathioprine. Ten-year all graft actuarial survival was 84%, 10-year actuarial graft survival in patients with primary renal disease 90%, and with subsequent graft after first HLA graft failed 97.5%, for age-matched population 98.5% (P=NS). Overall death rate was 8.7% (4/46); in secondary renal disease patients 50% (3/6); in primary renal disease patients 2.5% (1/40, P=0.004). All (9/9) HLA-identical second grafts functioned. Acute rejection with azathioprine/prednisone prophylaxis occurred in 55% (9/17) of grafts treated with <6 pre-graft blood transfusions, with the same prophylaxis but >5 units in 12% (2/16, P=0.015), and with cyclosporine prophylaxis in 13% (2/15, P=0.021). Pulse steroids alone reversed all acute rejection. Grafts failed in 6.2% (3/48), all in primary renal disease patients and one from technical one noncompliance, and one chronic rejection. Graft cost/patient/year amortized over 9 years is $3,855 and comparable dialysis cost would be $35,650; cost for all patients on dialysis for 9 years would be $11,293,320 while comparable graft cost was 1,221,418, a savings of 89.2%. Our conclusions are that HLA-identity associates with the following: (1) a 10-year actuarial survival in primary renal disease that equals that of the age-matched population, (2) uniform success in repeat grafts, (3) virtual absence of chronic rejection despite a high incidence of acute rejection in azathioprine/prednisone grafts that (4) always reversed on pulse steroids, and (5) a cost reduction for grafting of 93.2% compared with dialysis therapy.

Evaluation of aerobic Bactec 6A non-resin- and 16A resin-containing media for the recovery of microorganisms causing peritonitis.

Recovery of microorganisms causing peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) continues to be problematic. To date, there is no universally accepted protocol. We prospectively analyzed 430 peritoneal effluent specimens by three protocols: (a) 3 ml of effluent was centrifuged and the pellet plated onto blood and MacConkey agars and into thioglycolate broth (routine method), (b) 3 ml of each was inoculated at the bedside into Bactec 6A aerobic and 16A aerobic resin-containing media, and (c) 3 ml of each was inoculated in the laboratory into Bactec 6A and 16A media. Of the peritoneal effluent specimens, 104 (24%) had microorganisms recovered; 63 were positive by the routine method compared with 86 (P < .001) by bedside-inoculated 16A. Bedside-inoculated 16A (86) recovered more microorganisms than bedside-inoculated 6A (70) (P < .05). Laboratory-inoculated 16A (78) recovered more organisms than the routine method (63) (P < .05). Of 42 positive peritoneal effluent specimens delayed in transit > or = 1 day, 23 were positive by the routine method compared with 34 bedside inoculated 16A (P < .01) and 30 laboratory-inoculated 16A (P > .114). Bedside-inoculated 16A media is superior to the routine method for the recovery of microorganisms causing peritonitis in CAPD patients.

HLA matching enhances long-term renal graft survival but does not relate to acute rejection.

Forty patients with end-stage chronic renal failure received living donor renal grafts, matched at more than 1 HLA haplotype, over the last 25 years. Of these grafts, 33 were first and 7 were second grafts. All recipients received prophylactic corticosteroids. Thirty-four also received prophylactic azathioprine, and 6, prophylactic cyclosporine. Acute rejection occurred in 65% (11/17) of non-cyclosporine treated grafts when the recipient was given 5 or fewer units of blood preoperatively, but in only 18% (3/17) when more than 5 units were given. High-dose steroid therapy reversed the acute rejection each time. Chronic rejection occurred in 2 grafts. Irreversible rejection did not occur in any second graft. Chronic glomerulonephritis, possibly due to recurrent disease, occurred in 1 graft. Five grafts have been lost, 1 each from technical and immunosuppressive complications, and 3 from incidental death. The 1-year actuarial graft survival rate is 95% and the 10-year rate 84%. All surviving patients lead normal lives without significant health restriction, and employ minimal medication. It is postulated that: 1) acute cellular rejection is HLA-independent, and chronic rejection is HLA-dependent, and 2) hyperacute and chronic rejection are related and are parts of a spectrum of humoral immunity.

Bilateral traumatic renal artery thrombosis.

A case of bilateral traumatic renal artery thrombosis involving three renal arteries is presented. Four other cases of this entity are summarized for comparison. The recommended course of investigation is outlined, and the urgency of immediate surgical intervention is emphasized.

Early acute rejection of renal homografts: a characteristic clinical syndrome.

Seven of 74 patients with early functioning cadaveric renal homografts developed acute oliguric renal failure after the second but before the ninth day post-transplantation. The syndrome characteristically begins with an abrupt and simultaneous decrease in creatinine clearance, urine volume and urine sodium concentration. After a variable period and despite a reduction in immunosuppressive therapy, a diuretic phase ensues and renal function is restored. Complications associated with the syndrome include groin hematoma, pulmonary edema and renal rupture with shock. Renal rupture does not require nephrectomy: if the hemorrhage is controlled, the transplanted organ will resume function. Angiographic studies show normal nephrograms, stretched arterial vasculature and filling defects in the veins. Percutaneous renal biopsy shows interstitial edema and hemorrhage, venous congestion and tubular necrosis. Evidence is presented to support the hypothesis that this is a form of rejection occurring as the result of injury to the renal venous system.

Clinical value of cadaveric renal homotransplantation.

Cadaveric renal transplantation was found to be potentially applicable to 80% of a uremic population as observed over a six-year period. Death prior to presentation of a donor kidney occurred in 25%, 40% have received transplants and 15% are awaiting transplantation. Transplantation resulted in restoration of near normal renal function and homograft survival rates of 45% at one year, 40% at two years and 17% at four years. Failure of the therapeutic procedure resulted more often from death of the patient than from failure of the donor organ. Patient death was most frequently ascribed to complications of the immunosuppressive therapy, but cardiovascular accidents were also a significant cause. Early renal failure was due to hyperacute or acute rejection, while the cause of late renal failure remains unproved. Re-transplantation was effective treatment for late failure and, as a result, the four-year patient survival is nearly 40% compared to four-year initial kidney survival of 17%.

Experiences with high doses of furosemide in renal disease and resistant edematous states.

Six cases of edema, three due to the nephrotic syndrome, one to congestive heart failure and two to chronic renal failure, are reported in which furosemide was administered in oral doses higher than those usually prescribed (up to 720 mg. a day), in order to obtain a satisfactory diuresis. In one case of severe prerenal failure secondary to cardiogenic shock and in one case of acute tubular necrosis secondary to hypotension at the time of operation, intravenous doses up to 990 and 1400 mg. per day respectively were able to reverse the oliguria. In eight additional patients who were on chronic hemodialysis, furosemide was administered to the amount of 1000 mg. per day orally in divided doses for two weeks, and produced a moderate diuretic response.The use of high doses of furosemide in edema and renal failure resistant to the usual therapeutic measures appears to be safe and effective.

Late failure in cadaveric renal allografts.

Sixteen patients with renal cadaveric allografts who have survived for one year or longer are reported. The patients were analyzed from the standpoint of incidence, quantity and course of proteinuria in relation to renal function and the nature of the original disease.This analysis shows that proteinuria is progressive and is accompanied by a decline in renal function when the original disease is of an immune nature. This was not so in patients with non-immune original disease. These findings suggest that recurrence of original disease plays an important role in late failure of cadaveric renal allografts.