Effect Of Unilateral Nephrectomy Research Articles

Myocardial work indices in living kidney donor population

Abstract Funding Acknowledgements Type of funding sources: None. Background Living kidney donors represent a very special group of patients who are screened for cardiovascular morbidity preoperatively and remained with mildly reduced renal function after unilateral nephrectomy. The effect of unilateral nephrectomy on cardiovascular disease progression or subclinical cardiac dysfunction is still controversial. Myocardial deformation imaging allows left ventricular function quantification beyond ejection fraction. Non invasive assessment of myocardial work (MW) is a novel, promising speckle tracking- based method which can provide us to detect subtle myocardial dysfunction with advantages of load independency. We aimed to assess the impact of mildly reduced renal function after kidney donation, on subclinical cardiac structural and functional status. Methods We included seventeen kidney donors and seventeen age and sex matched healthy controls. All participants underwent transthoracic echocardiography (TTE). In addition to standard TTE measurements, 2D speckle – tracking based strain analysis was performed for left ventricle (LV) and right ventricle (RV). We also calculated Global Work Index (GWI) as the area of LV pressure-strain loop as a product of strain and x systolic blood pressure. MW efficieny (MWE), Global Constructive Work (GCW) and Global Wasted Work (GWW) were also calculated. Results There was no difference between the patients and the control group, regarding conventional parameters such as LV ejection fraction, Tricuspidal annular systolic excursion (TAPSE) and systolic pulmonary artery pressure. Left ventricular global longitudinal strain (GLS) and right ventricular global longitudinal strain were both significantly reduced in patient group (LV GLS ; -17,4% ,-19% p = 0,002 , RV GLS -19%, -24% p= 0,002 ). We found GWI and GCW were significantly lower in patients (mean 1549 mmHg% to 1800 mmHg%, p = 0,008) (mean 1857 mmHg% to 2176 mmHg%, p = 0,008), while GWW and MWE did not differ between the groups. We could not detect any significant correlation between MW indices and glomeruler filtration rate(GFR), time after surgery or hypertension. Conclusion Kidney donation may be associated with increased risk of subclinical cardiac dysfunctions. Myocardial Work might be a valuable diagnostic tool to detect subtle cardiac changes in this unique population.

Value of ambulatory blood pressure monitoring in potential renal donors - A prospective observational study

Introduction: Hypertension is very common among urban as well as rural population. In our donor selection policy, uncontrolled hypertension or target organ damage is a contraindication to kidney donation. Studies of blood pressure (BP) response to unilateral nephrectomy in kidney donors in short- and long-term are needed. We studied BP in kidney donors by ambulatory BP monitoring (ABPM) and the effect of unilateral nephrectomy on BP in them for 1 year following kidney donation. Methodology: We enrolled 80 consenting kidney donors aged between 20 and 65 years and followed them serially at pre, 6, and 12 months postkidney donation. Estimated glomerular filtration rate (eGFR) was measured using chronic kidney disease exocrine pancreatic insufficiency (CKD EPI) formula. BP was measured in the clinic (sphygmomanometer) and by ABPM (MeditechABPM05). eGFR, two-dimensional echocardiography, ophthalmological fundus examination, and 24 h proteinuria measurement were done at each visit. Results: There was a significant difference in predonation systolic BP by clinic and ABPM (138.07 + 5.5 vs. 117.17 + 10.2; P 50 years and higher body mass index. Proteinuria increased from the baseline value of 82.7 ± 29.94–104.07 ± 49.36 mg/day at 1 year of follow-up. Conclusions: ABPM provides a more accurate and reproducible estimate of BP compared to clinic BP to rule out WC hypertension and MH in kidney donors. Unilateral nephrectomy has no significant impact on kidney function or proteinuria over 1 year.

EFFECT OF UNILATERAL NEPHRECTOMY ON KIDNEY FUNCTION IN FERAL DOMESTIC CATS (Felis catus)

This experimental study was conducted to determine the effect of unilateral nephrectomy on kidney function through hematological and urological values after surgery using feral domestic cats. Four (4) apparently healthy stray male cats were caught and used as experimental animals in this study. The animals were grouped into two (2) with two cats in each group. Grouping of the animals was based according to age, the 1st group – ages one year and above (>1 year) and the 2nd group – ages one year and below (<1 year). A split plot randomized complete block design was used in the experiment. The result shows that rectal temperature and packed cell volume have been affected on both age group of cats and other urological values like the presence of urobilinogen, protein, leukocytes, erythrocytes and crystals were elevated twenty four hours after surgery. A significant increase on the level of creatinine and blood urea nitrogen has been noted from the 3rd and 15th post – operative day. However, no significant difference was noted between experimental animals and the two age groups, all of which have similar result. The findings of the study revealed that the remaining kidney could not completely compensate the function of the other kidney up to the 15th post – operative day, it may take longer than fifteen days. Hence, proper supportive treatment, post-operative care & management of animals subjected to unilateral nephrectomy is a must and should continue beyond fifteen days.

Effect of unilateral nephrectomy on urinary angiotensinogen levels in living kidney donors: 1 year follow-up study.

Background:Urinary angiotensinogen (uAGT) has recently been proposed as a marker of kidney injury and activated intrarenal renin–angiotensin system. We investigated the effects of living donor nephrectomy on uAGT levels, blood pressure, estimated glomerular filtration rate, proteinuria and compensatory hypertrophy in the remaining kidney of living kidney donors.Methods:Twenty living kidney donors were included in the study and followed for 1 year. uAGT levels were measured with enzyme-linked immunosorbent assay preoperatively and postoperatively at the 15th day, 1, 6 and 12 months.Results:Four donors were excluded from the study due to lack of data. The mean baseline estimated glomerular filtration rate was 98 ± 15 ml/min/1.73 m². Serum creatinine, uAGT/creatinine, uAGT/protein levels were higher and estimated glomerular filtration rate was lower than baseline values at all time periods. Urinary protein/creatinine levels increased after donor nephrectomy, but after 6 months they returned to baseline values. Renal volume increased after nephrectomy, but these changes did not show any correlation with uAGT/creatinine, uAGT/protein, estimated glomerular filtration rate or systolic/diastolic blood pressures. uAGT/creatinine at 6 months and urinary protein/creatinine ratio at 12 months showed a positive correlation (P=0.008, r=0.639).Conclusion:After donor nephrectomy, increasing uAGT levels can be the result of activation of the intrarenal renin–angiotensin system affecting the compensatory changes in the remaining kidney. The long-term effects of increased uAGT levels on the remaining kidney should be examined more closely in future studies.

The Effects of Unilateral Nephrectomy on Blood Pressure and Its Circadian Rhythm.

Objective Hypertension and diurnal blood pressure (BP) variation are widely accepted as risk factors for renal damage. However, the effects of unilateral nephrectomy on BP and its circadian rhythm have not yet been clarified in patients with a compromised renal function, including dialysis patients. Methods We investigated 22 unilateral nephrectomized patients (16 men and 6 women, age: 64.5±14.3 years). The function of the circulating renin-angiotensin system (RAS) (plasma renin activity and plasma angiotensin II) and 24-h ambulatory BP monitoring (ABPM) were evaluated before and after nephrectomy. Daytime and nighttime 24-h ABPM values were determined based on sleep and waking times. Results In non-dialysis patients, the estimated glomerular filtration rate after nephrectomy was significantly lower than that before (before, 62.4±23.2 mL/min/1.73 m2 vs. after, 43.7±16.8 mL/min/1.73 m2; p<0.01). No significant differences were noted in the levels of BPs and circulating RAS before and after nephrectomy. However, the night-to-day (N/D) ratio of systolic BP (SBP) was significantly higher after nephrectomy than before (before, 93.3±6.5% vs. after, 98.4±6.9%; p<0.01), and the patterns of circadian BP rhythm also significantly differed before and after nephrectomy (p=0.022). Namely, the rates of dipper patterns decreased and nondipper and riser patterns increased after nephrectomy. In contrast, in dialysis patients, no significant differences were observed in the N/D ratio of SBP or the patterns of circadian BP rhythm before and after nephrectomy. Conclusion Unilateral nephrectomy affects the circadian rhythm of BP but not absolute values of BP.

Effects of unilateral nephrectomy on renal function in male Spontaneously Diabetic Torii fatty rats: a novel obese type 2 diabetic model.

The Spontaneously Diabetic Torii (SDT) fatty rat is a new model for obese type 2 diabetes. The aim of the present study was to investigate the effect of 1/2 nephrectomy (Nx) on renal function and morphology and on blood pressure in SDT fatty rats. Male SDT fatty rats underwent 1/2 Nx or a sham operation (Sham). Subsequently, animals were studied with respect to renal function and histological alterations. Induction of 1/2 Nx in SDT fatty rats led to functional and morphological damage to the remnant kidney and to hypertension, which are considered main characteristics of chronic kidney disease, at a younger age compared with the sham group. In conclusion, the SDT fatty rat is useful in investigations to elucidate the pathogenesis of human diabetic nephropathy and in new drug discovery.

Effect of unilateral nephrectomy on the pharmacokinetics of amikacin in humans.

As unilateral nephrectomy is not a rare surgical procedure, it gives rise to the question whether drugs predominantly eliminated through the urinary tract can be handled effectively by the remaining kidney. Amikacin is predominantly excreted via glomerular filtration with only a small fraction undergoing tubular reabsorption, and can be used as a model drug of glomerular elimination. The study was carried out in 28 subjects, 10 one month and 10 one year after unilateral nephrectomy, as well as in 8 healthy subjects. The pharmacokinetics of amikacin was investigated after a 1-h infusion of 5 mg kg(-1) amikacin. Blood samples were collected for 24 h after the end of infusion. Pharmacokinetic parameters of amikacin were calculated using a one-compartment open model for intravenous administration. Amikacin concentrations were significantly elevated in nephrectomized patients as compared with control subjects, both 1 month and 1 year after the surgery, and were similar at these two time-points following unilateral nephrectomy. Pharmacokinetic parameters of amikacin in patients subjected to unilateral nephrectomy were significantly different from those observed in the control subjects. As compared with the controls, an increase in AUC (area under the serum concentration-time curve) by 81% (P < 0.001) and 63% (P < 0.01) 1 month and 1 year after nephrectomy was observed, respectively. The lambda(z) (elimination rate constant) was reduced by 39% (P < 0.001) after 1 month and by 38% (P < 0.001) 1 year after the operation and t 1/2 was prolonged by 70% (P < 0.001) and by 43% (P < 0.01) at the respective time-points following unilateral nephrectomy. CLT (total body clearance of the drug from plasma) and CL(BW) (clearance per kg body weight) were both significantly decreased in unilaterally nephrectomized subjects in comparison with the controls. CLT and CL(BW) were reduced by 53% (P < 0.001) and 42% (P < 0.01) 1 month after nephrectomy, and by 45% (P<0.001) and 42% (P<0.01) 1 year after the surgery, respectively. No significant differences among studied groups were found in C0 (initial serum drug concentration) and Vd (apparent volume of distribution). The results suggest that unilateral nephrectomy impairs elimination of amikacin, and possibly other drugs predominantly eliminated via glomerular filtration.

A Prospective Observational Study of Changes in Renal Function and Cardiovascular Risk Following Living Kidney Donation

The effect of unilateral nephrectomy on the cardiovascular risk profile of living kidney donors has not been prospectively studied. We performed an observational cohort study of 58 living donors to 6 months postdonation for changes in 24-hr ambulatory blood pressure profiles, renal function, urine protein excretion, body mass index, glucose tolerance, and fasting lipid profiles. The 24-hr systolic blood pressure average and night-day ratio were unchanged from pre- to postdonation (118.9+/-11 vs. 118.1+/-14 mm Hg, P=0.77; 0.87+/-0.07 vs. 0.87+/-0.09, P=0.68, respectively). Estimated glomerular filtration rate declined from 91.9+/-16 to 61.6+/-12 mL/min/1.73 m2 (P<0.0001). Protein excretion, body mass index, glucose, and lipids were unchanged. No significant differences were noted between dippers and nondippers either pre- or postdonation. In summary, living kidney donation in the short term is safe. We suggest further observation of individuals with lower glomerular filtration rate for possible increased cardiovascular risk factors in the future.

Effect of unilateral nephrectomy on renal function of diabetic rats.

Glomerular alterations of experimental diabetes mellitus are observed in animals submitted to a reduction in renal mass, suggesting that some mechanisms responsible for the progression of renal disease are common. The aim of this study was to investigate the effect of nephrectomy on the renal function and morphology of diabetic rats. Male Wistar rats were divided into 4 groups: control (C), n=8; diabetic (DM), n=8; non-diabetic nephrectomized (Nx), n=8; (DMNx), n=9. DM was induced by streptozotocin (65 mg/Kg), and animals were treated with insulin. After 12 weeks, the glomerular filtration rate (GFR), renal plasma flow (RPF) and mean arterial pressure (MAP) were evaluated in unanaesthetized animals. Glomerular volume (GV), glomerular sclerosis index (GSI), mesangial volume density (Vvmes) and glomerular capillary surface density (Svcap) were also evaluated. Results show that kidney weight increased in Nx groups, being higher in DMNx. GFR was higher in Nx groups as was RPF, being higher in DMNx. RVR was lower in Nx groups, especially in DMNx. MAP was not different among the groups. RPF and GFR showed a high correlation for the DMNx group (r=0.95, p=0.02). The DMNx group showed a correlation between RVR and GFR (r=-0.96, p=0.005). The GV increased in Nx groups, and the GSI was higher in DMNx. Vvmes and Svcap increased in DMNx group. In summary, Nx groups developed similar degrees of glomerular hypertrophy, but only DMNx showed an increased value for GSI. The present data suggest that the acceleration of glomerular lesions in DMNx animals was more closely associated to hemodynamic adaptations than to glomerular hypertrophy.

Effect of Unilateral Nephrectomy on the Pharmacokinetics of Atenolol in Humans

Unilateral nephrectomy is a common surgical procedure and involves functional adaptation of the remaining kidney. There is a paucity of data addressing whether drugs eliminated predominantly through the urinary tract, such as atenolol, can be effectively handled by unilaterally nephrectomized patients. This study was carried out in 28 subjects 1 month (10 subjects) and 1 year (10 subjects) after unilateral nephrectomy, as well as in 8 healthy volunteers who were administered atenolol as a single oral dose of 100 mg. Pharmacokinetic parameters of atenolol were calculated using a one-compartment open model. It was revealed that atenolol blood serum concentrations were significantly elevated in nephrectomized patients as compared with the control subjects, especially 1 month after the surgery. Patients nephrectomized 1 month prior to the study were characterized by an increase in AUC by 43% (p < 0.05), reduction of lambda z by 36% (p < 0.001) and CLT by 27% (p < 0.001), and prolongation of t1/2 by 60% (p < 0.001) in comparison with healthy volunteers. The values of atenolol pharmacokinetic parameters in patients 1 year after unilateral nephrectomy did not differ significantly as compared to the controls. However, a trend indicating an impaired elimination was noted. A decrease in lambda z by 16%, prolongation of t1/2 by 32%, and reduction of CLT by 32% were observed. The results suggest that unilateral nephrectomy impairs elimination of atenolol and possibly other drugs predominantly eliminated via the kidney.

Effect of Unilateral Nephrectomy on the Pharmacokinetics of Atenolol in Humans

Unilateral nephrectomy is a common surgical procedure and involves functional adaptation of the remaining kidney. There is a paucity of data addressing whether drugs eliminated predominantly through the urinary tract, such as atenolol, can be effectively handled by unilaterally nephrectomized patients. This study was carried out in 28 subjects 1 month (10 subjects) and 1 year (10 subjects) after unilateral nephrectomy, as well as in 8 healthy volunteers who were administered atenolol as a single oral dose of 100 mg. Pharmacokinetic parameters of atenolol were calculated using a one-compartment open model. It was revealed that atenolol blood serum concentrations were significantly elevated in nephrectomized patients as compared with the control subjects, especially 1 month after the surgery. Patients nephrectomized 1 month prior to the study were characterized by an increase in AUC by 43% (p < 0.05), reduction of Λz by 36% (p<0.001) and CLT by 27% (p < 0.001), and prolongation of t1/2 by 60% (p < 0.001) in comparison with healthy volunteers. The values of atenolol pharmacokinetic parameters in patients 1 year after unilateral nephrectomy did not differ significantly as compared to the controls. However, a trend indicating an impaired elimination was noted. A decrease in Λz by 16%, prolongation of t1/2 by 32%, and reduction of CLT by 32% were observed. The results suggest that unilateral nephrectomy impairs elimination of atenolol and possibly other drugs predominantly eliminated via the kidney.

Improved analysis of multivariate data by variable stability scaling: application to NMR-based metabolic profiling

Variable scaling alters the covariance structure of data, affecting the outcome of multivariate analysis and calibration. Here we present a new method, variable stability (VAST) scaling, which weights each variable according to a metric of its stability. The beneficial effect of VAST scaling is demonstrated for a data set of 1 H NMR spectra of urine acquired as part of a metabonomic study into the effects of unilateral nephrectomy in an animal model. The application of VAST scaling improved the class distinction and predictive power of partial least squares discriminant analysis (PLS-DA) models. The effects of other data scaling and pre-processing methods, such as orthogonal signal correction (OSC), were also tested. VAST scaling produced the most robust models in terms of class prediction, outperforming OSC in this aspect. As a result the subtle, but consistent, metabolic perturbation caused by unilateral nephrectomy could be accurately characterised despite the presence of much greater biological differences caused by normal physiological variation. VAST scaling presents itself as an interpretable, robust and easily implemented data treatment for the enhancement of multivariate data analysis.

The effects of organ resection on rat urinary bladder carcinogenesis.

The effect of unilateral nephrectomy, orchiectomy or partial hepatectomy on the growth of chemically induced rat bladder tumors was investigated. Male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 5 weeks, and surgical resection of one of these organs was performed 2 weeks after the completion of BBN administration. Histological evaluation of the bladder 24 weeks after the start of the experiment revealed that unilateral nephrectomy and orchiectomy significantly increased the numbers of preneoplastic and neoplastic lesions as compared with the corresponding sham-operated groups. Partial hepatectomy also enhanced tumor growth, although not significantly. Immunohistochemical studies examining the effect of organ resection on normal bladder urothelium showed that BrdU immunostaining of urothelial cells significantly increased 7 days after unilateral nephrectomy or orchiectomy, while BrdU incorporation was minimum after partial hepatectomy or sham operation. C-met expression in the bladder urothelium was evident following unilateral nephrectomy or partial hepatectomy, while increased immunoreactivity of androgen receptor was noted following unilateral orchiectomy. Further study is needed to determine the exact mechanism of the bladder tumor growth-enhancing effect associated with organ restriction.

Renal function in the noninsulin-dependent diabetic rat: Effects of unilateral nephrectomy

A new model of noninsulin-dependent diabetic (NIDD) is described which exhibits more prominent defects in renal function than does the standard neonatal NIDD model. To produce this model, 2-day-old neonatal male Wistar Kyoto (WKY) rats were injected intraperitoneally with streptozotocin (90 mg/kg; NIDD), while their corresponding nondiabetic controls were administered vehicle (citrate buffer, pH: 4.5; control). At 3 weeks of age, the animals were weaned, and 1 week later, under ether anesthesia, the animals underwent a right nephrectomy or a sham operation. Diabetes was confirmed by intraperitoneal administration of a glucose load (2 g/kg), which resulted in significantly higher blood glucose concentration in the NIDD, compared to the nondiabetic rats. Surgical reduction of renal mass had no effect on the glycemic response to a glucose tolerance test in either group. Intravenous administration of an isotonic saline load resulted in a similar pattern of enhanced sodium and fluid excretion in the two-kidney sham-operated nondiabetic and NIDD rats. These responses were significantly higher than those observed in their counterparts with one remaining kidney. Yet, the natriuretic and diuretic responses to the saline load were significantly lower in the nephrectomized NIDD, compared to the nephrectomized nondiabetic rats. The glomerular filtration rate was similar in the sham-operated (two kidneys) NIDD and nondiabetic rats. In contrast, both the basal and saline-stimulated glomerular filtration rate were lower in the nephrectomized NIDD rats compared to the nephrectomized nondiabetic group. Mean arterial pressure was similar between the two nephrectomized groups, thereby ruling out a significant contribution from the pressure-diuresis-natriuresis mechanism to the reduction in sodium and fluid excretion in the nephrectomized NIDD rats. Thus, unilateral nephrectomy is an effective method of accelerating the manifestation of NIDD-related renal alterations. The mild, but progressive, nature of diabetes in this model should facilitate the investigation of temporal changes in renal function in NIDDM.

Effect of unilateral nephrectomy on gene expression of metalloproteinases and their inhibitors.

Levels of mRNA encoding for metalloproteinase (MMP) 1, 2, 3 and 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were measured in both the renal cortex and glomeruli following unilateral nephrectomy or a sham operation. The expression of MMP-1 and MMP-3 increased 3-fold (p < 0.001) within the renal cortex 24 h following nephrectomy, and then gradually decreased to the control level after 7 days. In contrast, expression of MMP-2 and MMP-9 remained unchanged following nephrectomy. TIMP-1 mRNA levels also significantly increased 4-fold (p < 0.001) within the renal cortex 12 h following nephrectomy, followed by a decrease to the control level after 3 days. In contrast, the glomerular expression of MMP-1, -2, -3 and TIMP-1 remained stable while minimal MMP-9 mRNA was detectable. MMPs and TIMP-1 may be associated with the early stages of renal hypertrophy following unilateral nephrectomy.

Promoting effect of unilateral nephrectomy on urinary bladder carcinogenesis in rats.

The effect of unilateral nephrectomy on the growth of bladder tumors was investigated in male F344 rats treated with 0.05%N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine(BBN) for 6 weeks by means of macroscopical and microscopical examinations. Unilateral nephrectomy 4 weeks after the initiation of BBN administration significantly increased both the number and the volume of visible tumors per rat as compared with the sham‐operated group. Histological examination also revealed that the numbers of papillonodular hyperplasia and cancer per basement membrane were significantly increased by unilateral nephrectomy. The results imply a growth‐enhancing effect of unilateral nephrectomy on carcinogenesis of the rat bladder.

Unilateral Nephrectomy 24 Hours after Bilateral Kidney Irradiation Reduces Damage to the Function and Structure of the Remaining Kidney

The effect of unilateral nephrectomy 24 h after irradiation on renal function and death with renal insufficiency as well as histopathological changes in the kidney was assessed. Single doses totaling 8-18 Gy were given bilaterally to unanesthetized female and male C3Hf/Kam mice. Renal function damage was assayed by blood urea nitrogen (BUN) and hematocrit.(Hct). Histological damage was quantified by two parameters: kidney area and number of surviving tubule cells along the renal capsule. The number of glomeruli was scored as an indication of the number of nephrons. Changes in the two functional parameters did not appear sooner after irradiation in the nephrectomized mice than in the non-nephrectomized mice. Rather, less impairment of function was measured by both parameters in the nephrectomized mice but only after radiation doses greater than 12 Gy. The LD50 at 424 days after irradiation was also higher in the nephrectomized mice than that in the mice receiving only irradiation, 13.98 Gy (95% confidence limits = 12.03, 15.93) and 11.71 Gy (95% confidence limits = 10.4, 13.1), respectively, in agreement with the data on function. Unilateral nephrectomy alone induced a 10% increase in size of the contralateral kidney. The dose-response curve for the kidney area from nephrectomized mice was parallel to and displaced above that for non-nephrectomized mice, indicating that the increase in renal mass occurred independent of and was not compromised by radiation. Unilateral nephrectomy alone induced no increase in the number of proximal tubules in the contralateral kidney. However, tubule survival was higher in nephrectomized mice given doses greater than 12 Gy compared with mice receiving only radiation. Fitting the tubule survival data by maximum likelihood analysis gave D0's of 6.7 Gv (95% confidence limits = 6.3, 7.1 Gy) and 3.7 Gy (95% confidence limits = 3.5, 3.8 Gy) for the irradiated nephrectomized mice and irradiated mice, respectively. However, the number of glomeruli was the same for both groups, suggesting that the number of the nephrons did not change. These data suggest that the improvement in renal function in mice nephrectomized 24 h after irradiation of both kidneys compared to those receiving only irradiation was due to tubule hyperplasia and not renal hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

Pathogenesis of glomerular injury in the fawn-hooded rat: effect of unilateral nephrectomy.

Fawn-hooded (FH) rats with congenital proteinuria and systemic and glomerular hypertension are very susceptible to renal damage at a young age. In this study, the effects of unilateral nephrectomy (UNX) on the function and structure of the remaining kidney in the FHH substrain were assessed. A long-term study was performed to determine the changes in systemic blood pressure, renal function, and proteinuria during the development of chronic renal failure in UNX-FHH and two-kidney (2K) FHH rats. Renal micropuncture and morphologic studies were performed at 4 wk after surgery. The long-term study showed that, after UNX, systolic blood pressure did not differ significantly (from that of 2K-FHH rats. After UNX, there was compensatory hyperfiltration, at about 70% of the 2K level, that could be maintained for 12 wk only. The subsequent fall in GFR was preceded by severe proteinuria. The mean survival time of UNX-FHH rats was only 35 wk. Micropuncture studies showed that the high mean glomerular capillary pressure of 2K-FHH rats was further elevated after UNX. The glomerular capillary ultrafiltration coefficient did not differ significantly between UNX-FHH and 2K-FHH rats. The weight of the remaining kidney and the mean glomerular tuft volume in UNX-FHH were, on average, 36 and 31% greater than in 2K rats. The results indicate that the FHH rat is extremely vulnerable to the adverse renal effects of UNX.(ABSTRACT TRUNCATED AT 250 WORDS)

Uridine and cytidine nucleotide synthesis in renal hypertrophy: biochemical differences in response to the growth stimulus of diabetes and unilateral nephrectomy.

The effects of unilateral nephrectomy (UN) and streptozotocin (STZ) diabetes on the activities of enzymes involved in uridine and cytidine synthesis in early renal growth (3-14 days after stimulus to growth) have been compared. Measurements were also made of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) and of glucose 6-phosphate (G6P), UDP-glucose, and glycogen, in relation to phosphoribosyl pyrophosphate, ribonucleotide, and complex carbohydrate formation. There were striking differences in the activities of CTP synthetase, G6PDH, and 6PGDH in the two conditions, with a three-fold increase in all three enzymes at 3 and 5 days and a two-fold increase above basal values at 14 days of STZ diabetes. The UN group showed no significant change in CTP synthetase at any stage and the activity of G6PDH and 6PGDH only kept pace with renal growth. Changes in routes of uridine synthesis were less marked, with a more rapid rise in carbamoyl-phosphate synthetase (glutamine) and a lesser response of dihydroorotate dehydrogenase in the UN relative to the STZ-diabetic groups. The enzymes of complex II and of uracil phosphoribosyltransferase showed essentially similar patterns during renal hypertrophy in UN and STZ diabetes. The parallel increase in CTP synthetase, G6PDH, and 6PGDH in the kidney in diabetes, also known to increase in growth situations in hepatomas and in renal tumors, is discussed in relation to hormone signals involved in renal growth. The importance of the concentration of CTP, and thus of CTP synthetase, in the CTP-cytidyltransferase reaction, an enzyme with a high Km for CTP, makes the present observation of the striking increase in CTP synthetase in STZ diabetes of particular interest in relation to phosphatidylcholine formation and hormone signal transduction.

Renal metallothioein metabolism after a reduction of renal mass. I. Effect of unilateral nephrectomy and compensatory renal growth on basal and metal-induced renal metallothionein metabolism

The effects of unilateral nephrectomy and compensatory renal growth on renal metallothionein metabolism were evaluated in the present study. In rats, the renal content of metallothionein increased in proportion to the increase in renal mass after unilateral nephrectomy and compensatory renal growth. However, when zinc was used to induce the synthesis of renal metallothionein, the remant kidney in uninephrectomized (NPX) rats produced significantly greater amounts of metallothionein on a per gram kidney basis than a normal kidney in sham-operated (SO) rats. In both NPX and SO rats, zinc pretreatment caused metallthionein synthesis to increase primarily in the renal cortex aand outer stripe of the outer medulla. Zinc pretreatment also changed the pattern for the intrarenal accumulation of inorganic mercury in NPX rats. After pretreatment with zinc, the accumulation of inorganic mercury predominated in the renal cortex rather than in theouter stripe of the outer medulla in the NPX rats. In addition, both NPX and SO rats were afforded complete protection against the nephrotoxic effects of a low, toxic dose of inorganic mercury when they were pretreated with inorganic zinc. The protection is postulated to be related to the alteration in the pattern of renal accumulation of inorganic mercury. In conclusion, the capacity to synthesize metallothionein increases significantly in rats after they have undergone unilateral nephrectomy and compensatory renal growth. The increased capacity of the remant kidney to synthesize metallothionein may involve adaptive changes both in trancriptional and/or translationalontrols of metallothionein synthesis.