Search

Intrarenal hypoxia is an acknowledged factor contributing to the development of diabetic nephropathy. Hyperbaric oxygen (HBO) therapy is a well-known adjuvant treatment for several medical conditions, such as decompression sickness, infections, and wound healing. The underlying metabolic response of HBO is largely unknown. In this study, we investigated the effect of HBO on the intrarenal metabolic alteration in diabetes. Hyperpolarized [1- 13 C]pyruvate MRI was performed to assess intrarenal energy metabolism in normoglycemic controls and short-term (2 weeks) streptozotocin-induced diabetic rats with and without HBO for five consecutive days. HBO therapy blunted intrarenal lactate production, 3 days after the therapy, in both normoglycemic controls and diabetic rats without affecting either lactate dehydrogenase mRNA expression or activity. HBO therapy reduced lactate formation in both normoglycemic and hyperglycemic rats. These findings support hyperpolarized [1- 13 C]pyruvate MRI as a novel method for monitoring HBO therapy via the pyruvate to lactate conversion., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Modulation of xenobiotic metabolism, including cytochrome P-450 (CYP) enzyme activities, due to dietary intakes of cruciferous vegetables, has been described in animals and humans, and the induction of CYP1A enzymes is suggested mainly to be related to the content of indolyl glucosinolates in these vegetables. The aim of the present study was to evaluate the effects on specific CYP activities of various broccoli samples containing different levels of glucosinolates. Groups of rats were fed 1 of 8 broccoli samples from 2 cultivars grown at different conditions. Thirteen different glucosinolates were quantified. The content of the 4 major glucosinolates, glucoraphanin (GRAP), glucoiberin, glucobrassicin (GB), and neoglucobrassicin (NeoGB) varied 5.6-, 2.7-, 3.2-, and 6.6-fold, respectively, among the broccoli samples. Dietary broccoli induced the CYP1A enzyme activities, 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-demethylase (MROD), in rat liver, weakly in colon, but not in kidney. In concordance, the hepatic metabolism of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) to the proximate carcinogen N-OH-PhIP, a CYP1A-related activity, was enhanced by broccoli. The 7-pentoxyresorufin-O-depenthylase (PROD) activity, an assay for CYP2B1/2, was weakly induced in colon and kidney but not in liver by broccoli. The 2 beta-OH- and 6 beta-OH-testosterone hydroxylase activities were induced in liver microsomes, showing that broccoli increased CYP3A activity. The observed modulations of CYP activities depended clearly on the broccoli sample used, and significantly different responses were observed for different cultivars and growth conditions. These results indicate that modulation of CYP metabolism by broccoli may vary significantly in humans as well, as the content of glucosinolates and other active substances also varies between commercially available broccoli samples. The different effects depending on the vegetable sample eaten have to be considered in future experiments and dietary recommendations., (Copyright 2001 by W.B. Saunders Company)

Townes-Brocks syndrome (TBS) is a human genetic disorder with features including urogenital, limb, anal and cardiac malformations associated with mutations of the TBS gene, Hsal 1. To begin to understand the role of the Hsal 1 protein (p140) in both normal development and disease pathogenesis, both message and protein expression were evaluated in specific tissues associated with TBS. DNA sequence information for Hsal 1 predicts that this homeotic, Drosophila homologue (Sal) encodes a zinc-finger protein consistent with a transcription factor. mRNA for Hsal 1 was highly expressed in fetal kidney and brain, with detectable production in thymus and heart. p140 was found in fetal ureteric bud, fetal and postnatal renal tubular epithelium, and renal blastema. In the 14-week fetal testis, the Hsal 1 protein was specifically expressed in the testosterone producing Leydig cells while in adult gonads Hsal 1 was also found in both Leydig and Sertoli cells, spermatogonia of the testis, and granulosa cells of the ovary. Evaluation of Wilms tumor revealed consistently high expression of the gene product in the epithelial and blastemal components. These spatial and temporal patterns of expression for Hsal 1, and the phenotypic effects associated with TBS, suggest that Hsal 1 plays an important role in the development and functional maintenance of the kidney and gonads. Furthermore, the Hsal 1 gene product may play a part in the pathogenesis of specific neoplasms occurring in these organs in addition to its specific role in Townes-Brocks syndrome.

Purpose: This retrospective review describes the surgical management of consecutive patients with severe hypertension and ischemic nephropathy due to atherosclerotic renovascular disease., Methods: From January 1987 through December 1998, a total of 590 patients underwent operative renal artery repair at our center. A subgroup of 232 hypertensive patients (97 women, 135 men; mean age, 66 +/- 8 years) with atherosclerotic renovascular disease and preoperative serum creatinine levels of 1.8 mg/dL or more forms the basis of this report. Change in renal function was determined from glomerular filtration rates estimated from preoperative and postoperative serum creatinine. The influence of selected preoperative parameters and renal function response on time to dialysis and dialysis-free survival was determined by a proportional hazards regression model., Results: In all, 83 patients underwent unilateral renal artery repair and 149 patients underwent bilateral repair, including repair to a solitary kidney in 17 cases. A total of 332 renal arteries were reconstructed, and 32 nephrectomies were performed in these patients. After surgery, there were 17 deaths (7.3%) in the hospital or within 30 days of surgery. Advanced patient age (P =.001; hazard ratio, 1.1; 95% CI [1.1, 1.2]) and congestive heart failure (P =.04; hazard ratio, 2.9 CI [1.0, 8.6]) demonstrated significant and independent associations with perioperative mortality. With a change of 20% or more in EGFR being considered significant, 58% of patients had improved renal function, including 27 patients removed from dialysis dependence; function was unchanged in 35% and worsened in 7%. Follow-up death from all causes or progression to dialysis dependence demonstrated a significant and independent association with early renal function response. Both patients whose function was unchanged (P =.005; hazard ratio, 6.0; CI [2.2, 16.6]) and patients whose function was worsened (P =.03; hazard ratio, 2.2; CI [1.1, 4. 5]) remained at increased risk of death or dialysis dependence. For patients with unchanged renal function after operation, risk of death or dialysis demonstrated a significant interaction with preoperative renal function. In addition to severe preoperative renal dysfunction, diabetes mellitus demonstrated a significant and independent association with follow-up death or dialysis., Conclusion: Surgical correction of atherosclerotic renovascular disease can retrieve excretory renal function in selected hypertensive patients with ischemic nephropathy. Patients with improved renal function had a significant and independent increase in dialysis-free survival in comparison with patients whose function was unchanged and patients whose function was worsened after operation. These results add further evidence in support of a prospective, randomized trial designed to define the value of renal artery intervention in patients with ischemic nephropathy.

Objective: The purpose of this study was to compare the accuracy of main renal artery Doppler scanning interrogation and hilar analysis to diagnose hemodynamically significant renal artery disease., Methods: From January 1998 to August 1999, 41 patients had renal duplex sonography with both main renal artery interrogation and hilar analysis followed by angiography. They form the basis of this review. The sample consisted of 24 men and 17 women, with a mean age of 68.9 +/- 10.2 years, who provided 80 kidneys for comparative analysis. Significant renal artery disease revealed through angiography was defined as >/= 60% diameter-reducing stenosis or occlusion. Peak systolic velocity (PSV) (in meters per second) and the presence of poststenotic turbulence (PST) were determined from main renal artery interrogation. Acceleration time (AT) (in milliseconds) was measured by means of hilar analysis. Significant renal artery stenosis was defined by a PSV of 2.0 m/s or more and a PST or an AT more than 100 ms. Sensitivity analyses of both PSV and AT were examined, and 95% CIs were computed. Receiver operating characteristic curves were used to estimate optimal values for PSV and AT., Results: Angiography revealed hemodynamically significant fibromuscular dysplasia in 5 kidneys (4 patients), atherosclerotic stenosis >/= 60% in 48 kidneys (30 patients), and renal artery occlusion in 4 kidneys (4 patients). Kidneys with significant renal artery stenosis had a higher PSV (2.54 +/- 0.11 vs 1.28 +/- 0.08, P <.001) and AT (82.43 +/- 7.2 vs 30.0 +/- 2.8, P <.001) compared with those without stenosis. Compared with angiography, a PSV of 2.0 m/s or more and PST demonstrated a sensitivity of 91%, specificity of 96%, and overall accuracy of 92% for detection of significant renal artery stenosis. Two of five studies with false-negative results reflected diseased polar vessels. By contrast, AT of more than 100 ms had a sensitivity of 32%, specificity of 100%, and overall accuracy of 54%. Receiver operating characteristic curve analysis revealed a PSV of more than 1.8 m/s and an AT of 58 ms or greater as optimal values. With an AT of 58 ms or more, the sensitivity was 58%, and specificity was 96%, with an overall accuracy of 70%. There were no apparent associations between PSV or AT and type or location of renal artery lesion, serum creatinine level, or end-diastolic ratio., Conclusion: Main renal artery interrogation is an accurate screening test to detect significant stenosis or occlusion of the main renal artery. Hilar analysis alone does not provide sufficient sensitivity to be used as a sole screening study. Neither method detects the presence of renovascular disease associated with polar vessels.

Background: A decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population., Methods: A retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase., Results: There was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate "best-fit" model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness., Conclusions: These data suggest that three very preventable or treatable conditions-hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease-are highly associated with clinically important changes in renal function in an older population.

Purpose: Cystic dysplasia of the rete testis is a benign congenital lesion that can mimic testicular cancer. We report 6 cases, review the literature, discuss the embryological etiology and make management recommendations., Materials and Methods: The records and pathology reports of 6 boys presenting with cystic dysplasia of the rete testis at 5 institutions were reviewed, as was the relevant literature., Results: Of the 6 cases 5 presented as scrotal masses in previously healthy boys and 1 as an abdominal mass in a newborn with multiple congenital anomalies. One patient had been followed from birth for a multicystic dysplastic kidney and 4 were found to have an ipsilateral absent kidney during evaluation. Development of the contralateral side was normal in most cases., Conclusions: Cystic dysplasia of the rete testis is an unusual, benign congenital lesion that can mimic testicular cancer in presentation. The presence of ipsilateral renal anomalies, particularly renal agenesis, can suggest cystic dysplasia of the rete testis in the differential diagnosis preoperatively. Even if cystic dysplasia of the rete testis is suspected, we recommend inguinal exploration and early control of the spermatic cord in the event that neoplasia is identified. If possible, the goal of preserving as much normal testicular parenchyma as possible is desirable. Long-term followup for possible recurrence is recommended, particularly after local excision.

Female nondiabetic and streptozotocin diabetic Wistar rats received 200 units heparin two times daily by subcutaneous injection for 6 mo. Mesangial volume fraction was reduced in heparin-treated control (CH) compared with untreated control (C) animals (CH 0.18 +/- 0.02 vs. C 0.24 +/- 0.02, P < 0.05), but other histological parameters were similar. In the heparin-treated diabetic (DH) group, wet kidney weight was increased compared with the untreated diabetic (D) group (DH 1,156 +/- 39 vs. D 1,050 +/- 30 mg, P < 0.05), as were absolute, but not fractional, glomerular volume (P < 0.05) and capillary volume (P < 0.05). Basement membrane thickness (DH 193 +/- 3 vs. D 231 +/- 9 nm, P < 0.01) and mesangial/glomerular volume fraction (P < 0.001) were decreased. Urinary albumin excretion was increased in the heparin-treated control animals compared with control animals [CH 980 (range 150-4,448) vs. C 221 (range 86-654) micrograms/24 h, P < 0.001] and in the heparin-treated diabetic animals compared with the diabetic animals [DH 12,785 (range 4,495-29,520) vs. D 899 (range 450-1,335) micrograms/24 h, P < 0.001]. Thus the possibly deleterious increases in glomerular capillary volume and albumin excretion may negate the beneficial effects of heparin on mesangial and basement membrane structures.

Renovascular disease (RVD) in older patients can cause progressive renal insufficiency and even end-stage renal disease (ESRD). The frequency of this clinical problem is not well defined. Renal duplex sonography (RDS) correctly identifies the presence of RVD with an overall accuracy of approximately 95%. Therefore, the purpose of this study was to utilize RDS as a noninvasive tool to identify the presence of critical RVD (> or = 60% diameter-reducing stenosis or occlusion) in patients 50 years of age or older beginning renal replacement therapy. A total of 53 consecutive participating patients were prospectively interrogated. Complete interrogations occurred in 45 of the 53 patients (85%), and 92 of the 103 kidneys (89%). Critical RVD was noted in 10 of 45 patients (22%). RVD was bilateral in 5 patients, unilateral in 5 patients, and there were 4 renal artery occlusions noted. All patients with critical RVD were white (10 of 25 white patients or 40%). Total pack years of smoking as well as associated cardiovascular and cerebrovascular conditions were greater in those patients with critical RVD compared to those without. These results indicate that RDS remains technically feasible as renal blood flow and function decline. Unsuspected RVD possibly contributory to renal insufficiency exists in a significant number of primarily white patients 50 years of age or older beginning renal replacement therapy. These patients are generally smokers with a high frequency of associated extrarenal atherosclerosis The addition of RVD as a separate category of disease causing ESRD would improve U.S. Renal Data System ESRD classification. RVD should be recognized as a cause of ESRD.

Purpose: This retrospective review describes surgical management of dialysis-dependent ischemic nephropathy., Methods: From February 1987 through September 1993, 340 patients underwent operative renal artery (RA) reconstruction at our center. A subgroup of 20 patients (6 women; 14 men; mean age 66 years) dependent on hemodialysis immediately before RA repair form the basis of this report. Glomerular filtration rates (EGFR) were estimated from at least three serum creatinine measurements obtained 26 weeks before and after operation. A linear regression model was used to estimate the mean rate of change of EGFR before and after RA repair. Comparative analysis of kidney status and change in EGFR were performed. The influence of function response on follow-up survival was determined by the product-limit method., Results: Hemodialysis was discontinued in 16 of 20 patients (80%). For these 16 patients, postoperative EGFR ranged from 9.0 to 56.1 ml/min/1.73 m2 (mean 32.4 ml/min/1.73 m2). Two of 16 patients resumed hemodialysis 4 and 6 months after surgery. Discontinuation of dialysis was more likely after bilateral or complete RA repair (15 of 16 patients) versus unilateral repair (one of four patients; p = 0.01). Permanent discontinuation of dialysis was associated with a rapid preoperative rate of decline in EGFR (mean slope log(e) EGFR: -0.1393 +/- 0.0340 without dialysis; -0.0188 +/- 0.0464 with dialysis; p = 0.04, but NS after controlling for multiple comparisons). Immediate increase in EGFR after operation was inversely correlated with the severity of nephrosclerosis (rank correlation: -0.57; 95% confidence interval [-0.83, -0.10]). Follow-up death was associated with dialysis dependence; two deaths occurred among 14 patients not receiving dialysis, whereas five of six patients dependent on dialysis died (p < 0.01)., Conclusion: Surgical correction of ischemic nephropathy can retrieve renal function in selected patients dependent on dialysis characterized by a rapid decline in preoperative EGFR in combination with global renal ischemia treated by complete or bilateral renal revascularization. After RA repair, discontinuation of dialysis may be associated with improved survival rates when compared with continued dialysis dependence.

Objective: To study the effect of Captopril on ambulatory blood pressure, renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients., Design: Randomized, double blind placebo controlled study of two years duration., Setting: University clinic., Patients: Twenty-two patients without hypertension., Intervention: Patients received 50 mg Captopril or placebo twice a day., Measurements: Ambulatory blood pressure, renal function, extracellular volume, and echocardiographic indices of cardiac function and dimensions were assessed annually. Clinic blood pressure and urinary albumin excretion were measured every 3 months., Results: Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group (mean +/- SD) (baseline 93 +/- 4 and follow up 91 +/- 8 mmHg) and in the placebo group (96 +/- 7 and 97 +/- 10 mmHg, NS). Night/day ratio of blood pressure was unaffected. Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril (557 +/- 97 and 600 +/- 112 ml min-1) versus the placebo group (574 +/- 85 and 535 ml min-1, p = 0.05). Filtration fraction was reduced in the Captopril versus the placebo group (p < 0.05). Extracellular volume and echocardiographically derived parameters were unaffected. The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion (Spearmans r = 0.85, p < 0.05) unlike clinic mean arterial blood pressure (r = 0.33, p = 0.35)., Conclusion: Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril. Renal plasma flow was increased and filtration fraction reduced. A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements.

To estimate its clinically unsuspected prevalence among patients with renal insufficiency, renal duplex sonography (RDS) was used to estimate the presence of critical renal artery stenosis (RAS) in that population. Patients, aged 45 to 75 years, with a serum creatinine of greater than or equal to 2.0 mg% but without dialysis dependence, prior renal transplantation, or prior renal artery surgery were considered for RDS. Fifty-three patients who met criteria for study were randomly selected from the Section of Nephrology clinic files and each patient was contacted both by mail and by telephone. Twenty-five patients agreed to RDS, and renal artery anatomy was determined in 21 patients using standardized RDS techniques. These techniques have demonstrated an overall accuracy of 96 and 97 per cent when compared prospectively to conventional angiography during validity analyses in the authors' center. Results of RDS revealed significant findings in 5 of 21 patients (24%). Three patients demonstrated criteria for ischemic nephropathy (IN): one patient had RAS with contralateral renal artery occlusion confirmed by angiography, while 2 patients demonstrated unilateral RAS. An abdominal aortic aneurysm and unilateral hydronephrosis were discovered in the fourth and fifth patients. Evaluation of patient demographic data and functional parameters as predictors of IN revealed that the duration of renal insufficiency at the time of RDS and extra-renal organ-specific atherosclerotic damage were significantly different between the groups with and without IN. The authors preliminary findings suggest that unsuspected ischemic nephropathy may exist in a significant minority of patients with renal insufficiency.

Initial renal hypertrophy in experimental diabetes is prevented by administration of a long-acting somatostatin analogue octreotide (SMS). To investigate the long-term effects of SMS on renal hypertrophy and urinary albumin excretion (UAE), streptozotocin-diabetic and non-diabetic rats were treated with two daily subcutaneous injections of SMS (100 micrograms x 2) for six months. Untreated diabetic and non-diabetic animals were used as reference groups. No differences were seen between the two diabetic groups in respect to body weight, food intake, blood glucose levels, urinary glucose output, hemoglobin A1C(HbA1C), fructosamine, serum growth hormone (rGH) or creatinine clearance, but kidney weight (896 +/- 36 vs. 1000 +/- 24 mg, P less than 0.02), UAE (417 +/- 131 vs. 1098 +/- 187 micrograms/24 hr, P less than 0.02), kidney insulin-like growth factor I (IGF-I) (167 +/- 16 vs. 239 +/- 17 ng/g, P less than 0.01) and serum IGF-I (301 +/- 26 vs. 407 +/- 17 micrograms/liter, P less than 0.01) were all reduced in the SMS-treated diabetic animals when compared to the untreated diabetic group. In non-diabetic rats SMS reduced body weight (274 +/- 3 vs. 293 +/- 5 g, P less than 0.01), kidney weight (695 +/- 9 vs. 764 +/- 17 mg, P less than 0.01), UAE (83 +/- 29 vs. 364 +/- 114 micrograms/24 hr, P less than 0.02), kidney IGF-I (202 +/- 12 vs. 280 +/- 12 ng/g, P less than 0.01), serum IGF-I (428 +/- 21 vs. 601 +/- 54 micrograms/liter, P less than 0.01) and serum rGH (67 +/- 6 vs. 126 +/- 27 micrograms/liter, P less than 0.05) when compared to untreated controls. When kidney weights were expressed in relation to body weight no difference was found between SMS-treated and untreated controls, while the difference between SMS-treated and untreated diabetic animals was still present (P less than 0.01). In conclusion, chronic administration of SMS has abating effects on diabetic renal hypertrophy and UAE, and thus indicates that SMS may reduce development of diabetic kidney lesions in experimental diabetes. The long-term suppressive effects of SMS on renal enlargement and UAE may in part be mediated through reduction in circulating and kidney IGF-I levels.

In this article, we analyze the blood pressure (BP) threshold for the start of antihypertensive treatment in insulin-dependent diabetes mellitus (IDDM) patients, with particular emphasis on those with persistent microalbuminuria or proteinuria (incipient and overt nephropathy, respectively). In such individuals, there is a clear increase in the prevalence of hypertension and in actual measured BP values that is not observed in normoalbuminuric patients. In 94 young healthy adults (less than 45 yr of age), average mean +/- SD arterial pressure (MAP; diastolic + 1/3 pulse pressure) was approximately 90.0 +/- 8.1 mmHg, closely corresponding to large population studies. In microalbuminuric IDDM patients, MAP values between approximately 105 and approximately 95 mmHg have been found in different studies, and the level has progressively decreased in various studies between 1984 and 1990 with similar BP-measuring techniques. Somewhat higher values are seen in patients with proteinuria, who are also consistently characterized by reduced glomerular filtration rate (GFR). A clear correlation is found between MAP plotted against the increased rate of microalbuminuria (%/yr) in incipient nephropathy and against fall rate of GFR (ml.min-1.mo-1) in proteinuric patients. In the natural history of renal disease, different cutoff points in MAP for start of progression are observed: greater than 95 mmHg for the start of progression of microalbuminuria and greater than 105 mmHg for the decrease in GFR. During antihypertensive treatment, there is reduction or no progression in microalbuminuria with MAP of approximately 90-95 mmHg and only a limited fall in GFR with MAP of approximately 100 mmHg. However, certain antihypertensive drugs (angiotensin-converting enzyme inhibitors) may have specific renoprotective actions, reducing microalbuminuria at rather low BP levels or even independent of BP reduction. The optimal way of monitoring BP may be by 24-h ambulatory recording.

The kidney changes seen in rats shortly after the induction of experimental diabetes were reviewed: Kidney weight increases by 15 to 20% during the first 4 to 5 days of diabetes and by 70 to 90% after some weeks. GFR increases after a lag-time of some days in parallel to kidney weight. Morphometric analysis shows glomerular hypertrophy to be prominent during the first few days of diabetes. The glomerular filtration surface increases by 40% after 4 days. Diabetic renal hypertrophy is related to the severity of the diabetes, and kidney growth rate relates linearly to blood glucose. Moderate diabetes mellitus and unilateral nephrectomy have approximately the same effect on the kidney (weight increase 20%/4 days). When diabetes mellitus and nephrectomy are combined, renal growth rate almost doubles.

Normal and diabetic rats were given daily injections of human growth hormone for four days (5 mg per rat per day). Injected rats showed no differences from uninjected controls with respect to kidney weight or renal content of protein, RNA or DNA. Kidney weight increased by 7% after two days of diabetes and by 20% after four days, but growth hormone caused no augmentation of the hypertrophy. It is concluded that growth hormone plays no role in the initiation of diabetic renal hypertrophy.

Streptozotocin diabetic rats have larger kidneys than non-diabetic rats. In the present study the rate of kidney growth during the first seven days of diabetes was correlated with the blood glucose concentration. Over a wide range of blood glucose concentrations (116-340 mg/100 ml) the kidney weight, protein content and protein/DNA ratio were closely correlated with the glucose values.

Different renal structures were studied during the initial phases of compensatory renal hypertrophy. Four days after unilateral nephrectomy, kidney weight had increased by 31%, total glomerular volume by 17%, and glomerular filtration surface by 10%. After 24 days, kidney weight had increased by 44%, glomerular volume by 24%, and filtration area by 22%. The proximal tubules increased their cell volume and diameter significantly after four days (30% and 11%), but tubular length did not increase until later. We conclude that during compensatory renal hypertrophy glomerular growth is less pronounced than tubular growth, and that the increase in filtration surface area is not sufficient to explain the increased glomerular filtration rate after nephrectomy. Proximal tubules initially grow transversally and only later on longitudinally, the two growth phases possibly corresponding to cellular hypertrophy and hyperplasia.

25-Hydroxyvitamin D3 1 alpha- and 24-hydroxylase, NADPH-cytochrome c reductase, heme oxygenase, and ATPase activities were studied in viable kidney cells isolated from rats submitted to unilateral kidney damage (cortical electrocoagulation) and during the development of acute renal failure subsequent to excision of the contralateral undamaged kidney. Measurements of blood pH, plasma total and ionized calcium, phosphorus, creatinine, kidney histology, and phosphorus nuclear magnetic resonance spectroscopy determinations of phosphorus-containing compounds in kidney tissue were also performed. Seventy-two hours after unilateral kidney damage, no significant changes were observed in blood pH or in the plasma parameters studied. During this period, a significant increase in the activity of the 25-hydroxyvitamin D3 hydroxylases could be demonstrated in the cells of the contralateral undamaged kidney. A similar pattern of compensatory rise in the activity of the other enzymes studied was not detected. However, in the damaged kidney viable cells, the hydroxylase activities remained unchanged relative to those in sham-operated controls, despite a 5-fold increase in the inorganic phosphate content and a marked decrease in the organophosphorus and ATP content of this tissue. During the development of acute renal failure, a significant decrease in the activity of the hydroxylases occurred only when the rise in plasma creatinine concentration suggested severe renal insufficiency.

1. Kidney weight and content of protein, RNA and DNA were measured in rats with streptozotocin diabetes of varying duration. 2. Diabetic rats had larger kidneys than control rats: after 3 days of diabetes the weight increase was 15 per cent and after 42 days of diabetes it was 90 per cent. The protein content rose in parallel to the weight. 3 RNA content was already increased after 36 h of glycosuria, whereas DNA content was unchanged for the first 3 days of diabetes, and increased thereafter. The protein/DNA ratio increased rapidly during the first 3 days but remained constant thereafter. 4. Insulin treatment decreased the renal weight gain by about 67 per cent during the first 8 days of diabetes, but did not prevent the increase in DNA. When insulin was started after 25 days of diabetes there was only a slight regression of kidney growth.

Glomerular filtration rate (GFR) was measured by constant infusion of iothalamate in conscious rats with and without streptozotocin diabetes. Kidney weight had already increased significantly after 4 days of diabetes. GFR was unchanged at that time, but increased subsequently, so that GFR/kidney weight was normal after 1 month of diabetes. Tubular glucose reabsorption rate was increased to the same extent as kidney weight after 4 days of diabetes. It is concluded that renal growth in experimental diabetes cannot be initiated by glomerular hyperfiltration, but that increased glucose reabsorption may have a causal role.

Renal hypertrophy in rats with streptozotocin diabetes or after unilateal nephrectomy was studied by sterological techniques. -- After 4 days of diabetes total glomerular volume had increased by 30%, and after 47 days by 43%. Glomerular growth was more pronounced than whole kidney growth during the first 4 days, but subsequently whole kidney growth exceeded glomerular growth. In control rats glomerular volume was 4.9% of total kidney volume; after 4 days of diabetes it was 5.4% and after 47 days 4.1%. -- Proximal tubule length increased from 366 m/kidney in control rats to 447 m/kidney after 47 days of diabetes; tubular luminal diameter increased from 26.8 micrometer to 31.4 micrometer in the same rats. Tubular length and luminal diameter were, however, not increased after 4 days of diabetes. -- In unilaterally nephrectomised rats there was no early rapid glomerular growth. Glomerular fractional volume was 4.9% in controls, 4.4% at four days, and 4.2% at 24 days after nephrectomy. -- The results indicate a disturbed glomerulo-tubular balance in the early phases of diabetic renal hypertrophy.