Gender-related differences in advanced glycation endproducts, oxidative stress markers and nitric oxide synthases in rats

An age- and blood pressure-associated increase in methylglyoxal (MG) and MG-induced advanced glycation endproducts (AGEs), including N(epsilon)-carboxyethyl-lysine (CEL) and N(epsilon)-carboxymethyl-lysine (CML), in the kidney of spontaneously hypertensive rats (SHR) has been shown. In the present study, gender-related changes in AGEs and nitric oxide synthase were investigated in Sprague-Dawley (SD) and stroke-prone SHR (SHRsp) rats. Immunohistochemical analyses were conducted on kidneys from 24-week-old male and female SD rats as well as SHRsp. The systolic blood pressure of SHRsp was significantly higher than that of SD rats. Male SD rats had more intense kidney staining for CEL than female SD rats. Both male and female SHRsp had more marked CEL and CML staining localized to kidney tubules, as opposed to SD rats. Female rats showed more staining in glomerular vessels than male rats in both SD and SHRsp. Nuclei containing nuclear factor-kappaB (NF-kappaB) p65 and activated macrophages were seen in the kidney from SHRsp, not so much in SD rats, localized to renal tubules in male and glomerular vessels in female SHRsp. A higher protein level of NF-kappaB p65 was found in SHRsp than in SD rats. SD rats had more intense kidney neuronal nitric oxide synthase staining than SHRsp. The intensity of inducible nitric oxide synthase staining was significantly higher in SHRsp than in SD rats, with no gender differences in either strain. SHRsp and male rats exhibited higher AGEs and oxidative stress than SD and female rats, respectively. These differences might partly account for the development of hypertension in SHRsp and the higher vulnerability of male animals to renal pathology.     

Mechanisms of posttransplant hypertension

Posttransplant hypertension is an important risk factor for cardiovascular mortality and graft function. We performed metabolic studies in 35 hypertensive patients with well-maintained graft function on maintenance immunosuppressive drugs and in 17 normotensive control transplant recipients. The group of hypertensive recipients were characterized by increased peripheral plasma renin activity, lack of change in blood pressure in response to salt loading and restriction, and by increased peripheral and renal resistance. In contrast, on the same protocol in a group of patients with essential hypertension, blood pressure fell significantly on a low-salt intake. Peripheral resistance in hypertensive transplant recipients fell in response to saline loading, in contrast to the effects in normotensive transplant recipients. Hypertensive patients with retained native kidneys as compared to those who had these removed prior to transplant, but were still hypertensive, differed only with regard to reduced renal plasma flow in the former group. These data are consistent with a predominantly renin-dependent hypertension in these renal transplant recipients. When bilateral nephrectomy or repair of graft renal artery stenosis is being considered, response to captopril may offer a means of selection; acute renal failure on captopril suggests functionally significant renal artery stenosis.     

Effects of Intercellular Adhesion Molecule-1 on Renal Damage in Spontaneously Hypertensive Rats

Aims: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory process and immune response. The aim of the study was to investigate ICAM-1 expression in the kidneys of spontaneously hypertensive rats (SHRs) and the relationship between the level of ICAM-1 and renal damage. Methods: Male Wistar–Kyoto (WKY) rat and SHR models were employed. Blood pressure (BP) was recorded using tail cuff method. Twenty-four hour proteinuria and β₂-microglobulin (β₂-MG) were measured using biuret method and radioimmunity kits, respectively. Biochemical parameters were measured after the animals were killed. ICAM-1 expression in renal tissue was assessed using western blot and real-time polymerase chain reaction (PCR). Results: It was observed that BP, proteinuria, and urine β₂-MG were more increased in SHR groups than that in the same age WKY groups. In SHR groups, BP, proteinuria, and urine β₂-MG at the 56th week were significantly higher than that at the 28th week. ICAM-1 protein and mRNA expression in SHR renal tissues was significantly increased in SHR groups compared with the same age in WKY rats. ICAM-l expression was positively correlated with proteinuria and urine β₂-MG. Conclusion: This study demonstrated that the renal expression of ICAM-1 was increased in SHR with renal damage, and inflammation may be involved in the hypertensive renal damage.     

Hypertension accelerates the pace of chronic graft dysfunction in the rat*

Abstract In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK → SHR) or an SHR (SHR → SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR → SHR developed a significantly higher blood pressure than BBOK → SHR. Blood pressure in BBOK → BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK → SHR) and SHR → SHR kidneys as compared with the BBOK → BBOK kidneys (P < 0.05). Infiltration of ED-1⁺ monocyte/macrophages and OX 19 pan-T-cells was most pronounced in allografts (BBOK → SHR) and was also increased in SHR → SHR as compared with BBOK → BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependentfactors are of greater important.     

Recipient hypertension potentiates chronic functional and structural injury of rat renal allografts

BACKGROUND: Systemic hypertension affects many allograft recipients, is an important risk factor for chronic graft dysfunction, and is linked to reduced graft survival. The condition may up-regulate the expression of inflammatory host cells and their products. These, in turn, may significantly injure vascular endothelium and other components of allografted kidneys. METHODS: Lewis rats received orthotopic F344 renal allografts, a standard model of chronic rejection. Renovascular hypertension was produced by placing a silver clip (0.25 mm) on the renal artery of the retained contralateral native kidney 4 weeks after transplantation. Sham-clipped rats served as normotensive controls. Four recipient groups (Gp) were studied: Gp 1, rats with an allograft plus a clipped native kidney; Gp 2, those with an allograft and a sham-clipped native kidney; Gp 3, isografted animals with a clipped native kidney; and Gp 4, those bearing an isograft and a sham-clipped native kidney. Systolic blood pressure and proteinuria were measured every 2 weeks for 24 weeks. Grafts were assessed serially for morphologic and immunohistologic changes. RESULTS: Systemic blood pressure rose to hypertensive levels in Gps 1 and 3 within a week of clipping but never increased in Gps 2 and 4. Proteinuria developed in hypertensive animals but remained at baseline in normotensive controls. Intimal thickening of allograft arteries progressed to luminal obliteration with extensive perivascular and interstitial fibrosis by 24 weeks. In contrast, vascular changes in isografts of hypertensive hosts were restricted to medial hypertrophy. Tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, platelet derived growth factor (PDGF), endothelin, Il-6, major histocompatibility complex (MHC) class II, and B7 were up-regulated in allografts in hypertensive hosts. Vascular deposition of immunoglobulin (IgG) was increased. These changes were markedly less pronounced in Gp 3 isografts and minimal in the kidneys of the normotensive animals of Gps 2 and 4. CONCLUSIONS: An experimental model is presented that examines the influence of recipient hypertension in the pathogenesis of chronic dysfunction and injury developing in rat renal allografts over time.     

Hypertension after renal transplantation

Hypertension is a common and serious complication after renal transplantation. It is an important risk factor for graft loss and morbidity and mortality of transplanted children. The etiology of posttransplant hypertension is multifactorial: native kidneys, immunosuppressive therapy, renal-graft artery stenosis, and chronic allograft nephropathy are the most common causes. Blood pressure (BP) in transplanted children should be measured not only by casual BP (CBP) measurement but also regularly by ambulatory BP monitoring (ABPM). The prevalence of posttransplant hypertension ranges between 60% and 90% depending on the method of BP measurement and definition. Left ventricular hypertrophy is a frequent type of end-organ damage in hypertensive children after transplantation (50–80%). All classes of antihypertensive drugs can be used in the treatment of posttransplant hypertension. Hypertension control in transplanted children is poor; only 20–50% of treated children reach normal BP. The reason for this poor control seems to be inadequate antihypertensive therapy, which can be improved by increasing the number of antihypertensive drugs. Improved hypertension control leads to improved long-term graft and patient survival in adults. In children, there is a great potential for antihypertensive treatment that could also result in improved graft and patient survival.     

Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation

BACKGROUND: Combined liver-kidney transplantation (LKT) is the accepted treatment for patients with liver failure and irreversible renal insufficiency. Controversy exists as to whether simultaneous LKT with organs from the same donor confers immunologic and graft survival benefit to the kidney allograft. This study compares the outcomes of simultaneous LKT with the contralateral kidneys used for kidney alone transplantation (KAT) or combined pancreas-kidney transplantation (PKT) to understand the factors that account for the differences in survival. METHODS: From October 1987 to October 2001, LKTs with organs from 899 cadaver donors were reported to the United Network for Organ Sharing; 800 contralateral kidneys from these donors were used in 628 KAT and 172 PKT recipients. These 800 paired control patients were the basis of this analysis. RESULTS: Graft and patient survival rates were lower among LKT recipients compared with KAT (P<0.001) and PKT recipients (P<0.001), because of a higher patient mortality rate during the first 3 months posttransplant. Among human leukocyte antigen-mismatched transplants, LKT recipients demonstrated the highest 1-year rejection-free survival rate (LKT 70%, KAT 61%, and PKT 57% ) (P=0.005 vs. KAT, P=0.005 vs. PKT). There was a lower incidence of renal graft loss resulting from chronic rejection among LKT recipients (LKT 2% vs. KAT 8% vs. PKT 6%, P<0.0001). CONCLUSIONS: Patients undergoing LKT exhibit a higher rate of mortality during the first year posttransplant compared with patients undergoing KAT and KPT. Analysis of the data indicates an allograft-enhancing effect of liver transplantation on the renal allograft.     

Racial differences in the incidence of hypertensive end-stage renal disease (ESRD) are not entirely explained by differences in the prevalence of hypertension

Blacks experience a disproportionate risk of end-stage renal disease (ESRD) compared with whites. The increased prevalence of hypertension in blacks has been suggested as an explanation for this increased risk. We were able to examine this possibility using hypertensive ESRD incidence rates in a population with well-characterized prevalence of hypertension and rate of its control. After adjusting rates of hypertensive ESRD for age, sex, and differences in the prevalence of hypertension by race, we found black:white (B:W) relative risk still to be increased. Prevalence estimates for moderate-severe hypertension and differences in the control of hypertension between the two race groups are of insufficient magnitude to explain the increase in adjusted relative risk. This observation provides further support for the possibility that there are racial differences in the susceptibility to renal damage from elevated BP, which may explain increased risk for hypertensive ESRD in blacks, or that hypertension is being erroneously diagnosed as the cause of ESRD in blacks when another cause is present.     

Possible causes and consequences of hypertension in stable renal transplant patients

Previous epidemiologic studies of hypertension in renal transplant patients have produced contradictory results. Therefore, the incidence and clinical setting of chronic hypertension were examined in 201 stable renal transplant patients using a multivariate approach. Hypertension was present in 52.7% of patients at one year, and in 46.3% at the time of last follow-up, 5.0 +/- 1.9 years (mean +/- SD) after transplantation. Among possible causative factors, discriminant analysis demonstrated that body weight, the presence of native kidneys, and variables linked to allograft function were most closely associated with hypertension at both one year and last follow-up. One year after transplantation, age, sex, pretransplant hypertensive nephrosclerosis, and diabetes were also independently associated with hypertension. However, renal function declined to a greater degree in hypertensive patients, and only body weight, the presence of native kidneys, and variables linked to allograft function were associated with hypertension at last follow-up. Results also demonstrated that hypertension was associated with elevated serum lipid levels and an increased likelihood of dying or returning to dialysis. Thus, these results suggested several important risk factors for hypertension and its consequences in renal transplant patients.     

N-Domain angiotensin I-converting enzyme expression in renal artery of Wistar, Wistar Kyoto, and spontaneously hypertensive rats

One of the most intriguing features in kidney transplantation is the finding that kidneys from hypertensive rats can transfer arterial hypertension on transplantation into normotensive rats. Some evidence also suggest that, in humans undergoing renal transplantation, the genotype of the donor kidney determines the blood pressure in the recipient. The renin-angiotensin-aldosterone system is the major etiological candidate in hypertension because it plays an important role in the control of cardiovascular homeostasis. Angiotensin-converting enzyme (ACE) cleaves the C-terminal from angiotensin I as well as from bradykinin. Thus, by generating the potent vasoconstrictor angiotensin II and by degrading the vasodepressor bradykinin, ACE is considered to play a role in blood pressure regulation. We have previously described the presence of N-domain ACE in urine of Wistar (W), Wistar Kyoto (WKY), and spontaneously hypertensive rats (SHR), all of which can hydrolyze the vasodilator peptide Angiotensin 1-7 and also the N-Acetyl-Ser-Asp-Lys-Pro, two peptides described as specific for N-domain ACE. These findings suggest that the 90 kd ACE isoform found in urine and in tissues of SHR is a possible genetic marker of hypertension. Based on the fact that the renal artery has an important role in the control of renal blood flow, we evaluated the presence of N-domain ACE in the renal artery of hypertensive and normotensive rats. Using Western blotting techniques on the renal arteries of W and WKY rats, we detected the 190-kd ACE (similar to somatic ACE) and also the 65-kd ACE previously described in urine and renal tissue as N-domain ACE. The 65-kd and 90-kd isoforms of ACE were also detected in renal arteries in SHR rats. Further studies are required to understand the role of 90-kd enzyme described as a possible local marker of hypertension, its contribution in angiotensin catabolism, and whether this abnormal form of the enzyme has any link with the development and transfer of hypertension after transplantation.     

Laparoscopic bilateral nephrectomy for renin-mediated hypertension

Hypertension arising from retained native kidneys complicates the management of recipients of renal transplants. Reluctance to administer angiontensin-converting enzyme inhibitor (ACEI) drugs to patients taking cyclosporine has reopened the question of performing native nephrectomies for poorly controlled, renin-dependent hypertension. We report the first published cases of simultaneous bilateral laparoscopic nephrectomies in 2 patients: 1 in preparation for living-related donor transplantation and the other ten months following cadaver transplantation in a patient whose end-stage renal disease was from malignant nephrosclerosis. Both had very severe hypertension resistant to multiple drugs and both became normotensive with little or no antihypertensive medication following nephrectomies. A bilateral nephrectomy is currently feasible using a laparoscopic approach.     

Genetic susceptibility to renal injury in hypertension.

Substantial evidence indicates that hypertension plays a predominant role in the progression of most chronic renal diseases including diabetic nephropathy. Nevertheless, significant differences are observed in the susceptibility to develop hypertension-associated renal damage between individuals, racial groups and animal strains despite comparable hypertension. Recent studies employing a variety of genetic methods both in humans and in experimental models, have provided strong support for the potential importance of genetic factors and have suggested that genes influencing susceptibility to renal damage may be inherited separately from genes that influence blood pressure. However, due to the genetic complexity involved in a multifactorial trait such as the susceptibility to hypertensive renal damage, very limited progress has been achieved thus far in attempts to link such susceptibility to specific genetic mechanisms, chromosome regions and/or candidate genes. It is anticipated that the rapid recent advances in molecular genetic techniques and the simultaneous use of multiple complementary strategies, as is currently under way, will greatly facilitate this search and provide fundamental new insights into the pathogenesis of hypertensive renal damage.     

Bilateral native nephrectomy improves renal isograft function in rats

Bilateral native nephrectomy has been suggested to improve renal allograft survival in man. This effect may be most prominent in patients experiencing acute tubular necrosis following transplantation. Thus, native kidneys may alter the course of ischemic acute tubular necrosis in the transplanted kidney. In the present studies, we utilized an experimental model of syngeneic transplantation in which rejection does not occur. We studied Lewis rat renal isografts transplanted into littermates following sham, unilateral or bilateral native nephrectomy. In a fourth group of rats, we evaluated the importance of native kidney excretory function by studying isografts transplanted into littermates with bilaterally obstructed native kidneys. Renal blood flow and excretory function were measured in vivo, eight days following transplantation. Renal excretory function of isografts transplanted into animals following bilateral native nephrectomy was similar to normal nontransplanted Lewis kidneys. The presence of either one or both functioning native kidneys significantly reduced isograft inulin clearance, PAH clearance, and blood flow. However, when isografts were transplanted into Lewis rats with bilaterally obstructed native kidneys, renal isograft inulin clearance and blood flow were not significantly impaired. Nontransplanted kidneys demonstrated "functional hypertrophy" following contralateral nephrectomy, with glomerular filtration rate and renal blood flow increasing by approximately 50%. In contrast, isograft glomerular filtration rate in animals following bilateral native nephrectomy was equivalent to that of single kidneys from normal animals with both kidneys in situ. However, renal blood flow of isografts from these animals increased to the same level as nontransplanted Lewis kidneys following contralateral nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

The kidney as a sensor of cardiovascular risk in essential hypertension

Renal damage as a consequence of uncontrolled arterial hypertension is well recognized. Antihypertensive therapy has come to very significantly decrease the vascular damage in the kidneys of hypertensive patients. However, prevalence of mild renal insufficiency remains present in a significant proportion of the hypertensive population. This is accompanied by a marked increase in cardiovascular risk, as a consequence of the clustering of other cardiovascular risk factors and of insufficiently controlled BP. Prevention and protection of renal and cardiovascular damage in these patients will be one of the most relevant tasks in the future.     

Renovascular hypertension in spontaneous hypertensive rats: an experimental model of renal artery stenosis superimposed on essential hypertension

Renovascular hypertension superimposed on essential hypertension, a condition encountered in the elderly, was studied. An experimental animal model consisting of a two-kidney one-clip Goldblatt preparation in the spontaneous hypertensive (SHR) rat, that would simulate this condition, was designed. A 0.25 mm silver clip was placed on the left renal artery of SHR male rats. The same procedure performed on WKY rats served as control. All experiments were performed on low, normal, and rich sodium diet. Systolic blood pressure (BP) was measured by tail-cuff method. Plasma renin concentration (PRC) was determined before and after clipping of the renal artery. Results were as follows: Mean systolic BP increased significantly in clipped rats fed with normal and rich sodium diets. SHR showed an increase from 144 +/- 3 (mean + s.e.m.) to 168 +/- 3 mmHg, and WKY rats showed an increase from 120 +/- 2 to 139 +/- 5 mmHg. There was a two- to threefold rise in PRC. A low-salt diet given prior to clipping prevented the appearance of renovascular hypertension despite a significant rise in PRC. We concluded that renal artery narrowing plays a significant role in the rise of BP in the basically essential type of hypertension.     

Association of donor hypertension and recipient renal function in living donor kidney transplantation: A single‐center retrospective study

Transplant centers now accept living donors with well‐controlled hypertension. Little is known whether hypertension in living donors affects recipient's kidney function. We aimed to examine potential differences in kidneys from hypertensive donors compared to normotensive donors with respect to renal function over 36 months and histologic findings at transplantation (T0) and 12 months after transplantation (T1). Retrospective single‐center analysis of 174 living donor‐recipient pairs (age > 18; transplantation date 1/2008‐3/2016). Hypertension in donors was defined as being on antihypertensive medication. All biopsies were assessed by the same blinded, experienced renal pathologist. Biopsies were scored for glomerulosclerosis, IFTA, and arteriosclerosis. Regression models were used to examine the relationship of donor hypertension with renal function and histologic changes. Hypertensive donors were significantly older than normotensive donors. Chronic changes such as tubular atrophy and atherosclerosis were more evident in kidneys from hypertensive donors at T0 as well as T1. Donor hypertension was independently associated with histologic changes at T0 and T1 but not with renal function over the follow period. Despite more pronounced histologic changes in kidneys from hypertensive living donors, these grafts exhibited a similar functional outcome. However, they subsequently might be at a greater risk and warrant thorough follow‐up care.     

Prenatal exposure to nicotine modifies kidney weight and blood pressure in genetically susceptible rats: a case of gene-environment interaction

BACKGROUND: Epidemiologic studies suggest that in utero exposure to maternal smoking is associated with elevated blood pressure (BP) later in life. Our aims were: (1) to examine effects of intrauterine exposure to nicotine on BP and hypertension target-organ size in rats; and (2) to investigate whether such effects depend on genetic background, by studying two genetically distinct strains of rats: the spontaneously hypertensive rat (SHR) and the normotensive Brown Norway (BN) rat. METHODS: Nicotine or saline was administered to dams via subcutaneous osmotic minipumps throughout gestation. In nine-week-old male offspring, we measured BP and heart rate, assessed the weight of kidneys and heart, and determined fasting levels of glucose, insulin, triglycerides (TG), and cholesterol. We also measured gene expression of the insulin-like growth factor (IGF) system in the liver and kidneys. RESULTS: SHR and BN offspring differed in their response to intrauterine exposure to nicotine. SHR exposed to nicotine (vs. saline) exhibited higher BP (P < 0.02) and serum cholesterol levels (P = 0.01), and lower kidney weight (P < 0.0001). In contrast, BN rats did not demonstrate differences between the nicotine and saline groups in these variables, but the nicotine-exposed BN rats showed a significant up-regulation in the gene expression of IGF-1 in the liver (P < 0.0001) and IGF receptor in the kidney (P = 0.006). CONCLUSION: These results suggest that intrauterine exposure to nicotine alters the cardiovascular system depending on the genetic background and, as such, supports the notion that the intrauterine environment interacts with genes in determining an individual's health later in life.     

Risk factors and outcome of hypertension in living related renal transplant recipients

Summary: Impaired allograft function is an important cause of hypertension in cadaveric renal transplant recipients. the risk factors for post-tranplant hypertension in living related transplant recipients with inherent good graft functions are likely to be different and have not been studied. In addition, controversy surrounds any independent effect hypertension might have on renal allograft functions. Four hundred and seventy three living related renal allograft recipients were retrospectively analysed to study the risk factors for development of post-transplant hypertension and its effect on graft outcome. Prevalence of hypertension was 76.1%. the presence of pre-transplantation hypertension was the most important independent risk factor for development of hypertension after transplantation. This suggests an important role of retained native diseased kidneys as a cause of hypertension. Other risk factors included: cyclosporin A immunosuppression, patient age less than 40 years and the presence of renal insufficiency at last follow up. Hypertension did not have any effect on patient or graft survival during the mean follow-up period of 20.1 ± 13.7 months; however, it was associated with an independent risk for the presence of renal insufficiency in the post-transplant period.     

Exsanguinous metabolic support perfusion--a new strategy to improve graft function after kidney transplantation

BACKGROUND: The compounding damage of warm ischemia (WI) followed by cold preservation is a major barrier in renal transplantation. Although the relative effect of WI is not yet well understood, therapeutic strategies have mostly focused on minimizing the pathology seen upon reperfusion from the cold. Our study was designed to examine the effect of restoration of renal metabolism by warm perfusion on graft survival and to investigate the compounding damage of WI. METHODS: Using a known critical canine autotransplantation model (1), kidneys were exposed to 30 min WI followed by 24 hr cold storage in Viaspan. They were then either reimplanted directly or first transitioned to 3 hr of warm perfusion with an acellular perfusate before reimplantation. Contralateral kidneys were subjected to 0, 30, or 60 min WI; 24 hr cold storage, and 3 hr warm perfusion. RESULTS: Transplanted kidneys that were warm perfused before reimplantation had both lower 24 hr posttransplant serum creatinine (median of 3.2 vs. 4.1 mg/dl) and lower peak serum creatinine (median of 4.95 vs. 7.1 mg/dl). Survival rate for warm perfused kidneys was 90% (9/10) vs. 73% (8/11). In the contralateral kidneys, metabolism was affected by the compounding damage of WI. Renal oxygen and glucose consumption diminished significantly, whereas vascular resistance and lactate dehydrogenase-release rose significantly with increasing WI. CONCLUSIONS: The results demonstrate a reduction of reperfusion damage by an acellular ex vivo restoration of renal metabolism. Furthermore, data from the contralateral kidneys substantiates the relative role of WI on metabolism in renal transplantation.     

Polycythemia after kidney transplantation: influence of the native kidneys on the production of hemoglobin.

3 patients with renal transplantation who developed polycythemia presented normalization of the hemoglobin levels immediately after nephrectomy of the native kidneys. This observation induced the authors to study the role of the native kidneys in the genesis of polycythemia in recipients of renal allografts. Comparison was made among 32 patients submitted to renal transplantation, with maintenance of native kidneys (group I) and among 31 under the same conditions, but without the native kidneys (group II). Both groups were comparable according to age, sex, rejection crisis incidence and immunosuppressive therapy. It was observed that the hemoglobin levels of group I were significantly higher (p less than 0.05 to p less than 0.005) than those observed in group II, from the 3rd to the 30th posttransplantation month, becoming comparable from the 36th to the 54th months. The hemoglobin production, measured by the kinetics of labeled iron (59Fe), was higher in patients of group I. The authors concluded that the native kidneys are responsible for the observed polycythemia after a kidney transplantation.