Native Kidney Disease Research Articles

Applications of Doppler Ultrasound in Transplant and Native Kidney Disease

Applications of Doppler Ultrasound in Transplant and Native Kidney Disease

Post-transplant hypertension in the rat: Effects of captopril and native nephrectomy

In patients with well-functioning renal allografts, the presence of diseased native kidneys appears to be a common cause of elevated blood pressure. We evaluated the role of native kidneys in post-transplant hypertension using a rat model in which the confounding variables of rejection and immunosuppression could be eliminated. To produce disease in native kidneys. PVG rats were subjected to 5/6 nephrectomy. Four weeks following renal ablation, these hypertensive animals were transplanted with kidneys from syngeneic PVG donors. Four weeks later, the effects of captopril and native nephrectomy on blood pressure and renal hemodynamics were examined. Animals with remnant native kidneys which received non-rejecting renal isografts had sustained hypertension, elevated plasma renin levels and reduced transplant function. In these animals, administration of captopril reduced systemic blood pressure. Despite the reduction in blood pressure, PAH clearance by the transplanted kidney increased markedly while GFR rose modestly. Removal of the remnant native kidney also acutely lowered blood pressure. However, compared to captopril, native nephrectomy produced a more marked increase in GFR without significantly affecting renal blood flow. In this model of post-transplant hypertension in the rat, elevated blood pressure and reduced isograft function are mediated by the diseased native kidney, in part through the effects of angiotensin II. These data suggest that ACE inhibitors and native nephrectomy may have beneficial hemodynamic effects in patients with post-transplant hypertension caused by native kidneys.

Immunohistologic analysis of human renal allograft dysfunction.

The value of percutaneous core needle biopsy in the immunohistological evaluation of renal allograft dysfunction was studied in 72 consecutive biopsies performed in 42 patients. The phenotypes of infiltrating cells mediating graft destruction were identified with monoclonal antibodies and immunoperoxidase staining techniques. Light microscopy, electron microscopy, and immunofluorescence staining were performed in all biopsies. Biopsies were divided into groups depending on their classification on the basis of standard histologic criteria, i.e., acute tubular necrosis (ATN), acute interstitial rejection, acute vascular rejection, chronic rejection and renal disease in native kidneys (RDNK) of nontransplant patients. Immunohistologic analysis of graft biopsies showed a significant increase in Leu 1 (pan-T cells), (P less than 0.001), Leu 2 (cytotoxic/suppressor cells) (P less than 0.001), and Leu 3 cells (P less than .05) in acute interstitial rejection. The expression of DR antigen was significantly increased in both acute (P less than .025) and chronic (P less than .05) rejection, when compared with the findings in ATN biopsies. Leu M1 (monocytes/activated T cells) and Leu 10 (B cells/macrophages) were significantly increased (P less than 0.05 and P less than .005, respectively) in acute interstitial rejection only. The helper/suppressor ratio of infiltrating cells showed no significant change in any clinopathologic category. There was no correlation between the cell populations infiltrating the graft and those monitored in the peripheral blood. Allograft mononuclear cell infiltrates in cyclosporine (CsA) vs. azathioprine-treated patients revealed significantly fewer Leu 2 (P less than .05) and Leu M1 (P less than .05) cell populations in CsA patients during acute rejection. In 32 of these 72 biopsies (44.4%), the biopsy results provided a direct contraindication to the use of steroids, by allowing differentiation between allograft rejection and other causes of graft dysfunction. A total of 38% of the biopsies yielded a histological diagnosis that contradicted the clinical pre-biopsy diagnosis. All allografts showing evidence of severe small vessel disease and/or antibody-mediated rejection eventually were lost. These data highlight the usefulness of needle biopsy material as a guide to the study of intragraft immune events and to clinical management of recipients.

Etiology and pathogenesis of hypertension following renal transplantation.

Hypertension is a common feature of end-stage renal disease (ESRD) and constitutes a major risk factor for accelerated cardiovascular disease and premature death. While a reduction in the incidence and severity of hypertension is one potential benefit of kidney transplantation, hypertension often remains as a problem after transplantation, even in recipients of wellfunctioning allografts. Despite many studies of the underlying etiologic factors, the mechanisms implicated in post-transplant hypertension are still incompletely understood. A number of variables, including status of the diseased native kidneys, steriod therapy, rejection, recurrence of original disease, activation of the renin-angiotensin system, sodium and calcium metabolism, and transplant renal artery stenosis may play a role in the etiology of hypertension after transplantation. Patients with persistent high blood pressure for more than 3 months after transplantation should be thoroughly investigated, with controlled sodium intake so that proper medical or surgical therapy can be implemented. Since sodium restriction, radionuclide renal scanning, renin levels, or responses to saralasin or captopril may not provide a clear index of various possibilities, an accurate differential diagnosis my also require invasive procedures such as arteriography and/or renal biopsy.

BENEFITS OF REMOVAL OF NATIVE KIDNEYS IN HYPERTENSION AFTER RENAL TRANSPLANTATION

To find out whether diseased native kidneys can be the cause of hypertension in patients whose allograft otherwise seems to function well, six such hypertensive renal transplant patients were investigated before and 4·5±1·5 (±SD) months after removal of their native kidneys. After nephrectomy mean arterial pressure fell considerably yet renal (allograft) plasma flow increased by 77% and vascular resistance of the allograft fell by 55%. Mean transverse cardiac diameter and electrocardiogram voltage measurements of left ventricular hypertrophy both improved significantly. Since the rise in renal plasma flow could be induced by giving captopril, an inhibitor of angiotensin II formation, to patients who had not had their native kidneys removed, the native kidneys seem to exert their effect on the allograft via the renin-angiotensin system. The improvement in allograft plasma flow after nephrectomy was maintained for more than 11/2 years. Administration of captopril after native nephrectomy did not further change allograft plasma flow. The findings suggest that in many carefully selected patients with post-transplantation hypertension native kidney nephrectomy offers tangible benefits.

Acquired renal cystic disease in renal transplant recipients.

End-stage kidneys are known to undergo cystic transformation in patients treated with long-term hemodialysis. Little has been published, however, on the occurrence of acquired renal cystic disease (ACD) in renal transplant recipients. The available clinical and histopathological data were gathered on 22 renal transplant recipients who had undergone either necropsy or nephrectomy. None of our patients exhibited cystic changes in their donor kidneys. However, 11 patients (50%) had ACD of the native kidneys while the remaining patients lacked ACD. The duration of dialysis prior to transplantation was significantly longer and the life of the functional transplant kidney was significantly shorter in the ACD group as compared to the noncystic group. The combined duration of ESRD (dialysis + transplantation), however, was comparable in the two groups. It thus appears that the presence of a functioning renal allograft somehow retards the evolution of cystic changes in the diseased native kidneys. 1 of the patients in the ACD group exhibited superimposed multifocal clear cell carcinoma of the affected kidney, while none of the patients in the noncystic group exhibited renal neoplasm.

Deficient feedback regulation of erythropoiesis in kidney transplant patients with polycythemia

Anemia of endstage renal failure improves shortly after kidney transplantation. However, in about 10% of transplanted patients polycythemia occurs. By use of a sensitive in vitro bioassay the pathogenetic role of erythropoietin (Ep) was investigated in 12 patients with post-transplant erythrocytosis (PTE), and compared to 12 non-PTE patients. The mean Ep of 160 mU/ml was significantly elevated in patients with PTE as compared to 25 mU/ml of 36 healthy controls, whereas, the mean Ep of 24 mU/ml in non-PTE patients did not differ significantly from healthy controls. To further elucidate the mechanism of inappropriate Ep production, selective venous catheterization of native and transplanted kidneys was performed in six patients. In four PTE patients the mean Ep in native kidney veins of 110 mU/ml was significantly higher than the peripheral Ep of 66 mU/ml, whereas, mean Ep in kidney graft veins was 51 mU/ml. In contrast, in two non-PTE patients no significant difference between mean Ep from native and transplanted kidney veins was observed. We conclude that some patients escape from normal feedback regulation either due to autonomous Ep production or due to feedback regulation at an elevated level of hematocrit and that inappropriate Ep production originates from the diseased native kidneys.

Surgical therapy for persistent hypertension after renal transplantation.

The presence of the original diseased native kidneys in renal allograft recipients is associated with an increased prevalence of persisting post-transplant hypertension. In 9 of 10 such transplant patients bilateral nephrectomy of these native kidneys, performed at least 1 year after successful transplantation of a renal allograft, resulted in improved blood pressure control. Although these 10 patients had higher peripheral plasma renin activity (PRA) than normotensive patients (5.9 +/- 1.3 ng/ml/hr versus 1.5 +/- 0.3 mg/ml/hr), selective renal vein renin measurements did not consistently demonstrate higher renin concentrations from the native kidneys. Removal of the original kidneys was beneficial even in some patients who had stenosis of the allograft artery demonstrated by arteriography.

ARE THE NATIVE KIDNEYS RESPONSIBLE FOR ERYTHROCYTOSIS IN RENAL ALLORECIPIENTS?

SUMMARY The development of erythrocytosis following renal transplantation has been reported to be caused by a number of factors. These include acute and chronic rejection, hydronephrosis and renal artery stenosis. In this study, seven patients were noted to have erythrocytosis with hematocrits ranging between 53.5 and 66%. Serum erythropoietin levels were elevated and ranged between 11 and 60 mU/ml with a mean of 31.9 mU/ml in six of seven patients. Selective catheterization of veins of native and transplanted kidneys in three patients revealed mean serum levels of 40.9 and 13.0 mU/ml, respectively. This suggests that excess erythropoietin is being produced from the diseased native kidneys. Bilateral nephrectomy in one patient cured erythrocytosis and dropped systemic levels of erythropoietin (EP) to 6.1 mU/ml. In four of the remaining five patients, hematocrits came down spontaneously to within normal over a 1- to 3- year period Consequently, it appears that in a number of transplant patients the retained diseased kidneys, having lost all excretory and concentrating function, may remain capable of functioning as endocrine erythropoietin-producing organs Patients with end stage renal disease on chronic hemodialysis almost invariably suffer a moderate to severe degree of anemia, the cause of which is rather complex and includes decreased red blood cell production and decreased red blood cell survival (1) Shortly after kidney transplantation, however, and in the presence of good to excellent kidney function, most if not all transplant patients overcome their anemic state; their hematocrits once again begin to build up to become normal or close to normal. In a number of instances, however, the development of erythrocytosis has been reported following transplantation. Contributing factors for this development include acute and chronic rejection (2), renal artery stenosis (3), hydronephrosis (4) and, on a few occasions, overproduction of erythropoietin by the native diseased kidneys (5) The purpose of this study is to report the occurrence of erythrocytosis in seven patients with good functioning kidney transplants, to determine the cause of erythrocytosis, and to discern the role and site of erythropoietin production in these patients

ARE THE NATIVE KIDNEYS RESPONSIBLE FOR ERYTHROCYTOSIS IN RENAL ALLORECIPIENTS?

The development of erythrocytosis following renal transplantation has been reported to be caused by a number of factors. These include acute and chronic rejection, hydronephrosis and renal artery stenosis. In this study, seven patients were noted to have erythrocytosis with hematocrits ranging between 53.5 and 66%. Serum erythropoietin levels were elevated and ranged between 11 and 60 mU/ml with a mean of 31.9 mU/ml in six of seven patients. Selective catheterization of veins of native and transplanted kidneys in three patients revealed mean serum levels of 40.9 and 13.0 mU/ml, respectively. This suggests that excess erythropoietin is being produced from the diseased native kidneys. Bilateral nephrectomy in one patient cured erythrocytosis and dropped systemic levels of erythropoietin (EP) to 6.1 mU/ml. In four of the remaining five patients, hematocrits came down spontaneously to within normal over a 1- to 3-year period. Consequently, it appears that in a number of transplant patients the retained diseased kidneys, having lost all excretory and concentrating function, may remain capable of functioning as endocrine erythropoietin-producing organs.