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PubMed2002

Kidney- and site-selective delivery of 5-fluorouracil utilizing the absorption on the kidney surface in rats.

The present study was undertaken to elucidate the kidney- and site-selective delivery of 5-fluorouracil (5-FU) utilizing the absorption on the kidney surface in rats. An experimental system utilizing a cylindrical diffusion cell attached to the right kidney surface was established. After intravenous administration of 5-FU, the concentration of 5-FU in the right and left kidneys was almost the same and was rapidly eliminated. After right kidney surface application of 5-FU, however, the concentration of 5-FU in the right kidney was significantly higher than in the left kidney and other tissues. The 5-FU concentration in four sites of the right kidney after intravenous administration was almost the same. In contrast, 5-FU was site selectively delivered in the kidney after kidney surface application. The blood concentration of 5-FU was low (<1.7 microg/ml) until 120 min after kidney surface application. The maximum blood concentration of 5-FU after kidney surface application was much lower than after intravenous administration.

Absorption↗
PubMed1999

Cadmium, mercury, and lead in kidney cortex of the general Swedish population: a study of biopsies from living kidney donors.

Cadmium, mercury, and lead concentrations were determined in deep-frozen kidney cortex biopsies taken from 36 living, healthy Swedish kidney donors (18 males and 18 females), who were 30-71 (mean 53) years of age. Information about occupation, smoking, the presence of dental amalgam, and fish consumption could be obtained for 27 of the donors. The samples (median dry weight 0.74 mg) were analyzed using inductively coupled plasma mass spectrometry, and the results were transformed to wet-weight concentrations. The median kidney Cd was 17 micrograms/g (95% confidence interval, 14-23 micrograms/g), which was similar in males and females. In 10 active smokers, the median kidney Cd was 24 micrograms/g, and in 12 who never smoked, it was 17 micrograms/g. The median kidney Hg was 0.29 micrograms/g, with higher levels in females (median 0.54 micrograms/g) than in males (median 0.16 micrograms/g). Subjects with amalgam fillings had higher kidney Hg (median 0.47 micrograms/g, n = 20) than those without dental amalgam (median 0.15 micrograms;g/g, n = 6), but kidney Hg was below the detection limit in some samples. Nearly half of the samples had kidney Pb below the detection limit. The median kidney Pb was estimated as 0. 14 micrograms/g. This is the first study of heavy metals in kidney cortex of living, healthy subjects, and the results are relatively similar to those of a few previous autopsy studies, indicating that results from autopsy cases are not seriously biased in relation to kidney metal concentrations in the general population. Cd concentrations in those who never smoked were relatively high, indicating considerable Cd intake from the diet in Sweden. The effect of dental amalgam on kidney Hg was as expected, although the reason for the difference in Hg levels between males and females is unclear.

Adult↗
PubMed1997

Effect of race on outcome following kidney and kidney-pancreas transplantation in type I diabetics: the South-Eastern Organ Procurement Foundation experience.

In this study we analyze the South-Eastern Organ Procurement Foundation (SEOPF) experience with kidney and kidney-pancreas transplantation in IDDM recipients and evaluate the impact of racial disparity on patient and graft outcome. Data obtained from 4413 kidney-alone and 884 pancreas transplants performed in White and Black type I diabetics at member institutions of SEOPF between 10/1/87 and 7/25/96 were analyzed. Survival data from 15,827 transplants performed during the same period of time in non-diabetics were available for comparison. A lesser proportion of pancreas recipients were Black compared to kidney-alone (12% vs 23%, p < 0.0005). Recipient race had no effect on patient survival in any of the groups studied. Kidney graft survival, on the other hand, was adversely affected by Black race in both non-diabetic and diabetic recipients of a kidney transplant but not in diabetics who received a combined pancreas-kidney transplant. As was the case for patient survival in diabetics, recipient race had no effect on pancreas graft survival. Cox Regression analysis showed that kidney-pancreas transplant (p = 0.034, RR = 0.49) and female recipient gender (p = 0.046, RR = 0.68) were associated with a lower risk of failure of the pancreas graft. The following factors were independent predictors of kidney graft outcome: Donor age (p = 0.0001, RR = 0.95), kidney-pancreas transplant (p = 0.0004, RR = 0.58), AB match (p = 0.001, RR = 0.86), DR match (p = 0.006, RR = 0.82), preservation time (p = 0.012, RR = 1.01), Black recipient race (p = 0.047, RR = 1.23) and living donor (p = 0.06, RR = 0.73). Our findings suggest that the effect of race on graft outcome observed in non-diabetic and, to a lesser extent, diabetic kidney-alone transplant recipients, is not present after kidney-pancreas transplantation.

ABO Blood-Group System↗
PubMed2000

Comparison of progression of macrovascular diseases after kidney or pancreas and kidney transplantation in diabetic patients with end-stage renal disease.

AIMS/HYPOTHESIS: The aim of the study was to examine the effect of pancreas-kidney transplantation on the progression of macrovascular diseases in Type I diabetic patients with end-stage renal disease. METHODS: The progression of cerebrovascular disease, coronary heart disease and peripheral vascular disease in uraemic patients with Type I (insulin-dependent) diabetes mellitus and who had had simultaneous pancreas-kidney transplantation was compared with that of recipients of a kidney transplant alone. Between 1986 and 1998 a total of 11 uraemic diabetic patients received a simultaneous pancreas-kidney transplantation and 10 diabetic patients a kidney transplant alone. All transplants functioned for at least 24 months, the mean observation period was 69 +/- 37 compared with 70 +/- 33 months in both patient groups. Macroangiopathic diseases were classified in four stages as described earlier. RESULTS: In the group with simultaneous pancreas-kidney transplantation progression of cerebrovascular and coronary heart disease was observed in four patients (36%) and progression of peripheral vascular disease in five subjects (45%). In the cohort with kidney transplant alone four patients (40%) showed progression of cerebrovascular and coronary heart disease and five progression of peripheral vascular disease (50%); the difference is not significant. Mean values of HbA1c (5.8 +/- 0.2 vs 7.5 +/- 0.6%, p < 0.001) and serum triglycerides (1.2 +/- 0.4 vs 2.0 +/- 1.0 mmol/l, p < 0.05) were significantly lower in the patients with pancreas-kidney transplantation than in the patient group with kidney transplant alone. Serum cholesterol concentrations and blood pressures were similar in both cohorts. CONCLUSION/INTERPRETATION: From our results we concluded that pancreas-kidney transplantation reduces risk factors for the development of macroangiopathy but fails to halt progression of macrovascular diseases similar to Type I diabetic patients with kidney transplant alone.

Adult↗
PubMed2005

Natural history of kidney graft survival, hypertrophy, and vascular function in end-stage renal disease type 1 diabetic kidney-transplanted patients: beneficial impact of pancreas and successful islet cotransplantation.

OBJECTIVE: Diabetes, hypertension, infections, and nephrotoxicity of certain immunosuppressive drugs (i.e., calcineurin inhibitors) can reduce functional survival of the kidney graft. Our aim was to evaluate survival, hypertrophy, and vascular function of the kidney graft in end-stage renal disease (ESRD) type 1 diabetic patients after transplant. RESEARCH DESIGN AND METHODS: The study population consisted of 234 ESRD type 1 diabetic patients who underwent kidney-pancreas (KP; 166 patients), successful kidney-islet (KI-s; 24 patients), and kidney (KD; 44 patients) transplant. Kidney size, graft survival, vascular function, and microalbuminuria were evaluated prospectively yearly for 6 years. Sixty-eight protocol kidney biopsies were performed routinely between 1993 and 1998 cross-sectionally (3.2 +/- 0.3 years from kidney transplant). RESULTS: The KP and KI-s groups had better cumulative kidney graft survival at 6 years than did the KD group (KP: 73%; KI-s: 86%; KD: 42%, P < 0.01). The KP group but not the KI-s/KD groups showed a persistent kidney graft hypertrophy up to 6 years of follow-up. A significant increase in creatinine levels from baseline to year 6 was evident in the KD group (1.58 +/- 0.08 to 2.78 +/- 0.44 mg/dl, P < 0.05) but not in the KP/KI-s groups. The KP/KI-s groups only showed a reduction of renal resistance index from baseline to year 6 (KP at baseline: 0.74 +/- 0.01 to 0.68 +/- 0.01%, P < 0.01; KI-s at baseline: 0.72 +/- 0.02 to 0.69 +/- 0.02%, P < 0.05). At year 6, an increase from baseline in urinary albumin excretion was observed only in the KD group (31.4 +/- 9.0 to 82.9 +/- 33.6 mg/l, P < 0.05). Preliminary data suggested that graft nitric oxide (NO) expression was higher in the KP/KI-s groups than in the KD group (data not shown). CONCLUSIONS: In ESRD type 1 diabetic patients, KP and KI-s compared with KD resulted in enhanced kidney graft survival, hypertrophy, and vascular function.

Adult↗
PubMed2002

Kidney allografts and remaining contralateral donor kidneys before and after transplantation: assessment by quantitative (99m)Tc-DMSA SPECT.

UNLABELLED: We used (99m)Tc-dimercaptosuccinic acid (DMSA) quantitative SPECT (QDMSA) to assess the function of kidneys before harvesting and after transplantation as well as the function of remaining donor kidneys. METHODS: Nineteen kidney donors underwent a baseline QDMSA study before nephrectomy. The allografts of these kidneys were studied in recipients at 1 wk, 1-2 mo, and 6-15 mo after transplantation. The kidneys remaining in 16 donors were studied at 1-2 mo and 6-15 mo after harvesting. The parameters obtained in each SPECT study included functional volume, concentration of (99m)Tc-DMSA per cubic centimeter of renal tissue, and total kidney uptake. Clinical evaluation and determination of serum creatinine levels took place at the same time as SPECT. RESULTS: On the basis of the clinical evaluation, 14 grafts had normal function and 5 were impaired. The mean +/- SD of kidney uptake values expressed as percentage of baseline values were 131% +/- 30% in normal grafts versus 57% +/- 5% in impaired grafts at 1 wk (P < 0.01), 173% +/- 57% versus 65% +/- 10% at 1-2 mo (P < 0.001), and 190% +/- 50% versus 69% +/- 14% at 6-15 mo after transplantation (P < 0.01). Uptake values in the donors' remaining kidneys were 159% +/- 27% of baseline values at 1-2 mo and 164% +/- 30% at 6-15 mo after nephrectomy. Allografts and remaining kidneys showed a similar increase in total kidney uptake as a result of an increase in both functional volume and concentration. CONCLUSION: QDMSA may be a noninvasive assessment tool in kidney transplantation from living donors.

Adult↗
PubMed1990

[Problem of kidney transplantation (on the 25th anniversary of the first successful transplantation of the kidney in the USSR)].

The first successful transplantation of a kidney from an alive relative donor in the USSR was performed by B. V. Petrovsky at the All-Union Research Institute of Clinical and Experimental Surgery (now the All-Union Surgery Research Center, AMS, USSR) on April 15, 1965. In November, 1965 he transplanted a cadaver kidney for the first time with a good outcome. The Center possesses an experience with 987 kidney transplantations to date, among which 101 were related transplantations. The authors discuss the progress made in this field of surgery in a period of 25 years. The longest survival period among recipients with a functioning related kidney is 22 years and among those with a cadaver kidney, 19 years. With the use of Cy A 86% of transplanted related kidneys and 76% of cadaver kidneys function for 12 months or longer. The authors discuss the advantages of a new original method for transorganic oxygen preservation of a kidney suggested by G. A. Asoyan, instrumental-functional methods developed at the Center for appraising the hemodynamics of the transplanted kidney and diagnosis of the rejection crisis, cyclosporine nephrotoxicity, and progress in the techniques of kidney transplantation and immunosuppressive therapy. The authors believe that further improvement in the results of allogeneic kidney transplantation is well-grounded.

Female↗
PubMed1994

Pulsatile kidney perfusion for evaluation of high-risk kidney donors safely expands the donor pool.

Pulsatile preservation of cadaveric kidney allografts allows effective organ preservation and the opportunity to obtain information about the quality of the organ during storage. The use of information obtained by measuring FLOW (ml/min) and renal resistance (mean perfusion pressure/FLOW (ml/min)) while kidneys are undergoing pulsatile perfusion offers quantitative data to determine suitability of an organ for transplant. This may be more accurate than the combination of demographic variables with past and current medical information that has been traditionally used to evaluate donor suitability. We have evaluated 82 kidneys that received a period of pulsatile preservation at our institution. Kidneys were from consecutive donors age > or = 42 years and were stratified into three high risk groups: donor age > or = 60 (48%), the presence of hypertension (52%), and IMPORT kidney (48%). All IMPORT kidneys were obtained through UNOS after the local center considered them unacceptable for transplant and none were 6-antigen match organs. Kidneys were discarded if they failed to have a FLOW > or = 70 ml/min or RR < or = 0.4. Twelve kidneys (15%) failed to meet these criteria and were discarded. All 12 kidneys were from donors age > or = 60 (p = 0.002). The average FLOW and RR of transplanted kidneys was 103 ml/min and 0.3283 respectively. Six of 69 (8.6%) transplanted organs required dialysis (ATN). No pump parameters predicted the development of ATN although 5 of 6 kidneys were IMPORTs. Recipient outcome data, including 72-hour urine output and day 10 serum Cr, were affected by organ risk group, but these did not impact on patient care.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Theoretical kidney volume versus real kidney volume: comparative evaluation in fetuses.

In order to present equations and normal growth curves of the theoretical kidney volume we studied 290 kidneys taken from 145 fresh human fetuses ranging in age from 13 to 36 weeks post-conception (WPC). The kidneys were evaluated in terms of greatest longitudinal length (L) superior pole width (SW), inferior pole width (IW), thickness (T) and real volume (RV). The theoretical kidney volume was calculated (ellipsoid formula: volume = length x width x thickness x 0.5236) by using SW, IW and the arithmetic mean between SW and IW. The assessment of the theoretical volume by using IW was well correlated with the real kidney volume. We found no statistically significant difference between right and left kidneys. During the second trimester (13 to 24 WPC) there was no difference in kidney volume between male and female fetuses. In the third trimester (25 to 36 WPC) male fetuses presented kidney volumes significantly greater than female fetuses. To evaluate the theoretical kidney volume in fetuses, one may use the IW, which is a quickly and easily obtained measurement. During the second trimester one may monitor the fetal kidney using equations and growth curves without taking the fetal sex into account. During the third trimester the fetal kidney volume must be evaluated using specific curves for male and female fetuses.

Embryonic and Fetal Development↗
PubMed2005

Cross-sectional assessment of the effect of kidney and kidney-pancreas transplantation on resting left ventricular energy metabolism in type 1 diabetic-uremic patients: a phosphorous-31 magnetic resonance spectroscopy study.

OBJECTIVES: To test whether left ventricular (LV) dysfunction affecting type 1 diabetic-uremic patients was associated with abnormal heart high-energy phosphates (HEPs) and to ascertain whether these alterations were also present in recipients of kidney or kidney-pancreas transplantation. BACKGROUND: Heart failure is the major determinant of mortality in patients with diabetic uremia. Both uremia and diabetes induce alterations of cardiac HEPs metabolism. METHODS: Magnetic resonance imaging and phosphorous magnetic resonance spectroscopy of the LV were performed in the resting state by means of a 1.5-T clinical scanner. Eleven diabetic-uremic patients, 5 nondiabetic patients with uremia, 11 diabetic recipients of kidney transplantation, and 16 diabetic recipients of combined kidney-pancreas transplantation were studied in a cross-sectional fashion. Eleven nondiabetic recipients of kidney-only transplant and 13 healthy subjects served as control groups. RESULTS: Uremic patients had higher LV mass, diastolic dysfunction, and lower phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio in comparison with recipients of kidney-pancreas or nondiabetic recipients of kidney transplant. In diabetic recipients of kidney transplant the PCr/ATP ratio was higher than in uremic patients but was lower than in the controls. Recipients of combined kidney-pancreas transplant had a higher ratio than uremic patients but no difference was found in comparison with controls. CONCLUSIONS: Altered resting myocardial HEPs metabolism may contribute to LV dysfunction in diabetic-uremic patients. In diabetic recipients of kidney transplantation, a certain degree of LV metabolic and functional impairment was found. In combined kidney-pancreas recipients the resting LV metabolism and function were not different than in controls.

Adenosine Triphosphate↗
PubMed2000

ETA receptor blockade induces fibrosis of the clipped kidney in two-kidney-one-clip renovascular hypertensive rats.

BACKGROUND: In two kidney-one clip renovascular hypertension (2K1C), blood flow is reduced in the clipped kidney leading to ischaemia. The non-clipped kidney is characterized by increased shear stress. Circulating Ang II is elevated. All these factors are stimuli of the paracrine renal endothelin system. Indeed, we demonstrated an activation of the renal endothelin system in the 2K1C rat model. METHODS: We analysed the effects of chronic treatment with the ETA receptor antagonist BQ-123 on blood pressure, heart rate, plasma renin activity, and on the progression of glomerulosclerosis, interstitial fibrosis and vascular remodeling in the clipped and non-clipped kidney. RESULTS: Long-term treatment with BQ-123 led to a fibrotic atrophy of the clipped kidney characterized by a significantly reduced weight of the clipped kidney compared to the clipped kidney of the placebo-treated group. Computer-aided image analysis revealed a markedly enhanced interstitial fibrosis of these clipped kidneys after long-term ETA blockade. The effects of ETA receptor antagonists on the non-clipped kidney were less pronounced. Neither blood pressure nor plasma renin activity were significantly altered by BQ-123 treatment. CONCLUSIONS: The present study indicates that long-term blockade of the activated endothelin system in the clipped kidney of rats with renovascular hypertension using an ETA receptor antagonist led to a fibrotic atrophy of the clipped kidney.

Animals↗
PubMed2005

Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death. A simple definition and classification of kidney disease is necessary for international development and implementation of clinical practice guidelines. Kidney Disease: Improving Global Outcomes (KDIGO) conducted a survey and sponsored a controversies conference to (1) provide a clear understanding to both the nephrology and nonnephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI), (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD. The K/DOQI definition and classification were accepted, with clarifications. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause. Kidney damage in many kidney diseases can be ascertained by the presence of albuminuria, defined as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens. GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. Kidney disease severity is classified into five stages according to the level of GFR. Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed.

Albuminuria↗
PubMed2005

B cell heterogeneity in the teleost kidney: evidence for a maturation gradient from anterior to posterior kidney.

The fish immune system is quite different from the mammalian system because the anterior kidney forms the main site for hematopoiesis in this species. Using transcription factor-specific Abs derived from the murine system, together with anti-trout Ig Abs and Percoll gradient separation, we analyzed B cells from trout kidney sections and compared them to those from spleen and blood. For this study, immune cells were separated by Percoll gradients, and the resulting subpopulations were defined based on expression of B cell-specific transcription factors Pax-5 and B lymphocyte-induced maturation protein-1, as well as proliferative and Ig-secreting properties. Comparison of kidney, blood, and spleen B cell subsets suggest that 1) the anterior kidney contains mostly proliferating B cell precursors and plasma cells; 2) posterior kidney houses significant populations of (partially) activated B cells and plasmablasts; and 3) trout blood contains resting, non-Ig-secreting cells and lacks plasma cells. After LPS induction of resting B cells in vitro, the kidney and spleen have a high capacity for the generation of plasma cells, whereas the blood has virtually none. Our results indicate that trout B cell subsets are profoundly different among blood, anterior kidney, posterior kidney, and spleen. We hypothesize that developing B cells mature in the anterior side of the kidney and then migrate to sites of activation, either the spleen or the posterior kidney. Lastly, our data support the notion that the trout kidney is a complex, multifunctional immune organ with the potential to support both hemopoiesis as well as humoral immune activation.

Animals↗
PubMed1992

Expression of differentiation antigens and growth-related genes in normal kidney, autosomal dominant polycystic kidney disease, and renal cell carcinoma.

Cellular differentiation and mRNA levels of genes involved in kidney growth were investigated in normal kidney cells, cyst-lining epithelial cells of polycystic kidney disease, and renal carcinoma cells (RCC). All cells comparatively studied exhibited an antigenic phenotype of proximal tubular cells as shown by the expression of a panel of brush border membrane enzymes and kidney-associated cell surface antigens. The epithelial developmental antigen Exo-1 was expressed in 50% to 80% of cyst-lining epithelia in polycystic kidney tissue and in 20% to 30% of polycystic kidney cells cultured in vitro. Normal kidney cells and RCC were negative under identical culture conditions. The expression of antigen Exo-1 is associated with hyperproliferation in an epithelial tissue compartment composed of cells which have not yet reached their terminal differentiation state. Increased amounts of mRNA of the growth factor receptor system of epidermal growth factor (EGF) receptor and its ligand transforming growth factor (TGF)-alpha were associated with the malignant phenotype of RCC. Increased expression of EGF receptor and TGF-alpha, although less prominent, were also observed in polycystic kidney cells compared with normal kidney cells. In conclusion, the expression of Exo-1 in cyst-lining epithelial cells of autosomal dominant polycystic kidney disease (ADPKD) and the altered regulation of TGF-alpha and EGF receptor in these cells contribute to the hypothesis that hyperproliferation is an underlying pathogenic mechanism of ADPKD.

Antibodies, Monoclonal↗
PubMed2004

Chronic kidney disease progression in native and transplant kidneys.

PURPOSE OF REVIEW: The present review addresses the recent literature demonstrating important differences in the rate of progression of kidney function decline between transplant recipients and patients with native kidney disease. It also highlights the need for prospective studies to determine the importance of nonimmune factors that are established risk factors for progression of native kidney disease in the transplant setting. RECENT FINDINGS: Transplant recipients establish modest levels of kidney function but have rates of kidney function decline that are slower than those in patients with native kidney disease. Continued improvements in long-term graft survival have not been achieved despite significant advances in immunosuppression. There is increasing observational evidence that nonimmune factors that play a causal role in progression of native kidney disease may also be important determinants of allograft decline. There are fundamental differences between transplant recipients and patients with native kidney disease that preclude extrapolation of evidence from native kidney disease to the transplant setting. SUMMARY: Transplant recipients are a unique group of chronic kidney disease patients. Prospective studies to determine the importance of nonimmune factors such as hypertension, proteinuria, dyslipidemia, diabetes, and anemia in the transplant setting are needed.

Disease Progression↗
PubMed1991

Effect of arginine depletion on glomerular and tubular kidney function: studies in isolated perfused rat kidneys.

The effect of L-Arg depletion on glomerular hemodynamics and tubular function of isolated rat kidneys perfused with a medium containing 21 amino acids has been studied. A cyclooxygenase inhibitor was added throughout for blockade of prostaglandin synthesis. Arg depletion caused significant (approximately 30%) reductions in renal perfusion flow rate (PFR, 13.9 +/- 1.2 vs. 19.8 +/- 0.6 ml.min-1.g (kidney wt-1), glomerular filtration rate (GFR, 598 +/- 79 vs. 924 +/- 42 microliters.min-1.g kidney wt-1), and urine flow rate (139 +/- 38 vs. 192 +/- 13 microliters.min-1.g kidney wt-1) compared with control kidneys, which were perfused with a physiological concentration of Arg (200 microM). Filtration fraction (FF) increased with Arg depletion (5.1 +/- 0.4 vs. 4.4 +/- 0.4%). Arg-depleted kidneys had a lower absolute sodium (TNa, 75.7 +/- 8.8 vs. 107.9 +/- 6.0 mumol.min-1.g kidney wt-1) and glucose reabsorption (T glucose, 3.7 +/- 0.6 vs. 5.6 +/- 0.5 mumol.min-1.g kidney wt-1), corresponding to a lower sodium and glucose filtration. Potassium handling and reabsorption of free water were not changed. Oxygen consumption (QO2) was lower in Arg-depleted kidneys (4.6 +/- 0.3 vs. 5.5 +/- 0.5 mumol.min-1.g kidney wt-1). The effects of Arg depletion were completely reversed by the addition of Arg (1 mM) at 120 min and partly reversed by the addition of citrulline (1 mM). Ornithine depletion or addition had no effect on PFR, GFR, FF, TNa, T glucose, and QO2. N omega-methyl-L-arginine, a specific inhibitor of nitric oxide endothelium-derived relaxing factor, produced the same effect as Arg depletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Increased availability of nitric oxide leads to enhanced nitric oxide dependency of tubuloglomerular feedback in the contralateral kidney of rats with 2-kidney, 1-clip Goldblatt hypertension.

The contralateral kidney of 2-kidney, 1-clip hypertensive (2K1C) rats is unable to escape the renal vasoconstrictive and sodium-retaining effects of increased circulating angiotensin II levels. Evidence is accumulating that renal function is relatively preserved by enhanced influence of NO in the contralateral kidney. In this study, we investigated (1) whether the high NO dependency of renal hemodynamics in the contralateral kidney is due to increased availability of NO or increased sensitivity to NO and (2) whether elevated NO activity dampens the actions of angiotensin II to enhance tubuloglomerular feedback (TGF) responses in the nonclipped kidney of 2K1C rats. To estimate whether the available NO is increased, the NO clamp technique was applied in rats that underwent sham operation (n=6) and in the contralateral kidney of 2K1C Sprague-Dawley rats (3 weeks old; 0.25-mm silver clip; n=6). During systemic infusion of nitro-L-arginine (L-NNA; 50 microg/kg. min(-1)), sodium nitroprusside (SNP) was infused in the renal artery and the rate was adjusted so that renal vascular resistance (RVR) was restored to baseline levels. In sham rats, RVR increased during L-NNA treatment from 17.2+/-2.0 to 33.0+/-3.6 U (P<0.01) and was restored to baseline values during SNP infusion (17.1+/-2.3 U); 9. 2+/-1.8 nmol/min of SNP was needed to restore RVR to baseline values. In 2K1C rats, RVR increased during L-NNA treatment from 16.7+/-1.1 to 53.4+/-3.5 U (P<0.01). This increase of RVR was significantly larger than in sham rats. RVR was restored to baseline values during SNP infusion (17.4+/-0.9 U); 26.0+/-4.3 nmol/min of SNP was needed to restore RVR to baseline values (P<0.05 versus sham). Furthermore, maximum TGF responses were assessed before and during late proximal tubular infusion of L-NNA in the kidneys of sham rats and the nonclipped kidneys of 2K1C rats. Control maximum TGF responses were 4.7+/-0.7 and 5.1+/-0.4 mm Hg in sham and 2K1C rats, respectively. During intraluminal L-NNA infusion, maximum TGF responses were 15. 4+/-0.9 mm Hg in sham rats and 22.2+/-2.5 mm Hg in 2K1C rats (P<0.05 versus sham). Finally, urinary NO(2)+NO(3) excretion in the nonclipped kidney was significantly higher than in the clipped kidney (P<0.05). In conclusion, (1) as assessed using the NO clamp, ambient intrarenal NO levels are increased in the contralateral kidney of 2K1C rats and (2) the NO dependency of the TGF system is enhanced. These experiments indicate that adaptations in NO activity lead to relatively low TGF responsiveness, which will offset the simultaneous sodium-retaining actions of angiotensin II on proximal tubular reabsorption and TGF responsiveness.

Analysis of Variance↗
PubMedDate not supplied

Can a living kidney donor become a kidney recipient?

The living kidney donor represents a good resource for kidney transplantation. These grafts display better function and long-term graft survival at 5 and 10 years of follow-up. Furthermore, living donors prefer the possibility to increase kidney donation for a large waiting list of patients with end-stage renal disease (ESRD). However, kidney donation is a major surgical procedure associated with benefits and risks. The risks of donation have been studied in large series of living donors to focus on morbidity and mortality rates associated with the surgical procedure. New surgical laparoscopic techniques promote living kidney donation. While the benefits to the recipient are obvious, those for the donor are subjective and not quantifiable. However, donors describe donation as a great experience in life. The risk of kidney donation may be divided into the perioperative and the long-term risks. The evaluate the long-term risks for kidney donors requires a long follow-up. The main source of kidney donors in our transplant center has been living-related and -unrelated donors, with a minor percentage of cadaveric donors. In this report we present four kidney donors who developed ESRD thereafter, three becoming kidney recipients.

Follow-Up Studies↗