Renal functional reserve in subjects with diabetes mellitus

Diabetic nephropathy develops in approximately 35% of patients with insulin-dependent diabetes mellitus (IDDM) and in a similar proportion of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, we remain at present unable to identify the susceptible subset prior to the development of microalbuminuria. Up to 25% of IDDM patients and a variable proportion of NIDDM patients manifest glomerular hyperfiltration in the first few years of diabetes. It has been debated whether this basal hyperfiltration is predictive of future renal disease and whether better prediction can be achieved by the use of the renal haemodynamic response to a protein meal, defined by some authors as renal reserve. The concept of renal functional reserve in patients with diabetes mellitus is complicated by the dependence of the GFR response on basal GFR, the influence of the prevailing metabolic conditions, and because the response differs to different stimuli. We review the factors affecting renal hemodynamics and renal hemodynamic responses in the context of supranormal, normal, and impaired renal function in diabetes. We conclude that although the measurement of renal functional reserve may help clarify important pathophysiological mechanisms, the assessment of basal GFR in clinical practice is all that is required for predictive and monitoring purposes.     

Decrease in glomerular filtration rate in Japanese patients with type 2 diabetes is linked to atherosclerosis

OBJECTIVE: We assessed the effects of atherosclerosis on the glomerular filtration rate (GFR) in patients with type 2 diabetes and who had micro- or normoalbuminuria. RESEARCH DESIGN AND METHODS: A total of 61 Japanese patients with type 2 diabetes were recruited from inpatients of Osaka City University Hospital. They ranged in age from 40 to 69 years (28 men and 33 women). Each subject collected a 24-h urine sample for quantitative analysis of albumin. Absence of albuminuria was defined as a urinary albumin excretion level of <30 mg/24 h (n = 36) and microalbuminuria as a level of 30-300 mg/24 h. The GFR was estimated using 99mTc diethylenetriamine pentaacetic renogram method. As indexes of atherosclerosis, we measured the intimal-medial thickness (IMT) and distensibility of the carotid artery using high-resolution B-mode ultrasonagraphy and an echo-tracking system. We measured the resistance index (RI) of the renal interlobar arteries by pulsed Doppler sonography. RESULTS: The clinical characteristics of type 2 diabetic patients with and without microalbuminuria did not differ except for duration of diabetes, which was longer in the patients with microalbuminuria. GFR also did not differ between the patients with and without microalbuminuria. GFR was significantly correlated with the patient's age (r = -0.256, P < 0.05), carotid IMT (r = -0.326, P < 0.05), carotid stiffness beta (r = -0.449, P < 0.001), and renal arterial RI (r = -0.365, P < 0.05). In multiple regression analysis, independent factors associated with GFR were carotid IMT (R2 = 0.108, P = 0.0102), carotid stiffness beta (R2 = 0.208, P = 0.0003), and renal artery RI (R2 = 0.130, P = 0.0043). CONCLUSIONS: The decline in GFR in type 2 diabetic patients in the early stages of nephropathy may be due in part to atherosclerosis.     

Lack of effect of captopril on glomerular hyperfiltration in normoalbuminuric normotensive insulin-dependent diabetic patients

The aim of the present study was to evaluate the effects of captopril on the glomerular filtration rate (GFR) and urinary albumin excretion rate (UAER) of normoalbuminuric normotensive insulin-dependent diabetes mellitus (IDDM) patients with and without glomerular hyperfiltration. Eleven normoalbuminuric (UAER < 30 micrograms/min) patients (age: 34.3 +/- 4.6 years: diabetes duration: 9.5 +/- 6.4 years) participated in the study. Six patients were considered to be hyperfiltering (GFR > or = 134 ml/min/ 1.73m2). GFR (51Cr-EDTA single injection technique), extracellular volume (ECV; distribution volume of 51Cr-EDTA), UAER (RIA) and metabolic and biochemical parameters were measured at baseline, after 6 weeks on captopril (25 mg p.o. twice daily) and after 6 weeks off captopril. Plasma renin activity (PRA; RIA), plasma aldosterone (RIA) and blood volume (51Cr red cell labeled) were measured at baseline and after 6 weeks on captopril. The baseline clinical and laboratory characteristics of hyperfiltering and normofiltering IDDM patients were similar. GFR did not change during the study (144.1 +/- 28.8; 139.7 +/- 21.8; 132.8 +/- 29.9 ml/min/1.73 m2) either in patients with hyperfiltration (164.6 +/- 20.7; 153.8 +/- 18.3; 148.6 +/- 31.0 ml/min/1.73 m2; n = 6) or without hyperfiltration (119.6 +/- 11.1; 123.2 +/- 11.9; 113.8 +/- 14.4 ml/min/1.73 m2; n = 5). Also, ECV (22.2 +/- 3.6; 21.5 +/- 4.3; 21.5 +/- 3.5 L/1.73 m2), UAER (3.9 [0.4-22.1]; 4.0 [0.2-11.4]; 3.7 [2.0-26.2] micrograms/min), systolic (112 +/- 13; 105 +/- 10; 111 +/- 11 mmHg) and diastolic (76 +/- 12; 72 +/- 9; 73 +/- 12 mmHg) blood pressure did not change. No difference in blood volume (60.8 +/- 10.4; 62.3 +/- 8.4 ml/kg) or plasma aldosterone (10.4 +/- 4.9; 7.7 +/- 3.8 ng/dl) was observed between baseline values and values after captopril use. PRA increased (2.4 [0.4-22.1]; 12.9 [2.2-41.1]ng/ml/h) at the end of 6 weeks on captopril (P = 0.002). Fasting plasma glucose, glycated hemoglobin, fructosamine, plasma cholesterol and potassium, 24 h urinary urea and sodium were similar during the study. These results were unchanged when patients with and without hyperfiltration were analyzed as separate groups. From baseline to the end of 6 weeks on captopril there was no correlation between change in GFR and change in glycated hemoglobin (r = 0.02, P = 0.96), systolic (r = 0.23; P = 0.49) and diastolic (r = -0.32, P = 0.32) blood pressure, urinary urea (r = 0.21; P = 0.53) and UAER (r = -0.16; P = 1.00). In conclusion, captopril has no effect on the GFR and UAER of normoalbuminuric normotensive IDDM patients irrespective of the presence of glomerular hyperfiltration.     

Exogenous norepinephrine induces an enhanced microproteinuric response in microalbuminuric insulin-dependent diabetes mellitus

Exogenous norepinephrine (NE) increases intraglomerular pressure in animal experiments, but it is unknown whether NE induces a microproteinuric response in humans. Moreover, it has not been studied whether possible microproteinuric and renal hemodynamic changes induced by NE are altered in insulin-dependent diabetes mellitus (IDDM) complicated by microalbuminuria. Therefore, the microproteinuric and renal hemodynamic responses to exogenous NE infusions were measured in eight matched normoalbuminuric IDDM patients (group D1), microalbuminuric IDDM patients (group D2), and control subjects (group C). As anticipated, mean arterial pressure (MAP)-NE dose-response curves were significantly shifted leftward in groups D1 and D2 compared with group C (P < 0.05), indicating a higher systemic NE responsiveness in IDDM. On separate days, NE or placebo was infused at individually determined NE threshold doses (T; delta MAP = 0 mmHg), 20% pressor doses (20% P; delta MAP = 4 mmHg), and pressor doses (P; delta MAP = 20 mmHg), with measurement of urinary albumin (UalbV), IgG excretion (UIgGV), GFR (by 125I-iothalamate), and effective renal plasma flow (by 131I-hippurate). At NE pressor dose, UalbV and UIgGV rose in all groups (P < 0.05 to 0.01), whereas urinary beta 2-microglobulin was unchanged. The increases in UalbV and UIgGV were more pronounced in the microalbuminuric group than in the other groups (P < 0.05). An NE dose-dependent fall in effective renal plasma flow and rise in filtration fraction were found in all groups (P < 0.05 to 0.001 for all), whereas GFR did not change significantly. The renal hemodynamic dose-response relationship was similar in the groups. In conclusion, exogenous NE acutely promotes glomerular protein leakage, and it is plausible that intraglomerular NE effects contribute to this phenomenon. The microproteinuric response is enhanced in microalbuminuric IDDM despite unaltered renal hemodynamic responsiveness, which may reflect a specific NE response or a general effect of vasopressor stimuli to promote glomerular protein leakage in patients with a preexistent defect in glomerular permselectivity.     

Synthesis of the esterified cerebroside in the epidermis of guinea pigs

BACKGROUND: The level of glomerular filtration rate (GFR) and its determinants in non-insulin-dependent diabetes mellitus (NIDDM) are currently controversial. DESIGN OF THE STUDY: We measured GFR and effective renal plasma flow (ERPF) in 121 consecutive NIDDM without evidence of overt diabetic nephropathy. Age varied from 28 to 70 years, 61.2% were women and known duration of NIDDM was 0-37 years. Hypertension was detected in 36.4% of patients and 47.8% had microalbuminuria. RESULTS: An inverse correlation was found between GFR and age, but not with known duration of NIDDM: It was a weak correlation (r = -0.41) but statistically significant (P < 0.001). The other variables considered were not significant by multiple stepwise regression analysis, but patients with lower GFR tended to have diabetic retinopathy more frequently. GFR was lower in hypertensive compared to normotensive patients (123 +/- 28.4 versus 136 +/- 32.5 ml/min/1.73 m2; P < 0.05), but was not different between patients with normal and elevated albumin excretion rate. ERPF also had an inverse correlation with age (r = -0.45, P < 0.001). CONCLUSION: We conclude that (i) age should be considered as a confounding variable when evaluating GFR in patients with NIDDM, and (ii) the age-dependent decline in GFR may mask hyperfiltration in the early stages of diabetic nephropathy in NIDDM:     

Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes

The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposition to essential hypertension. We investigated whether this allele also confers increased susceptibility to nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). A group of 380 patients who had had IDDM for 15 to 20 years were genotyped at the angiotensinogen 235 locus. Included were 75 patients with normoalbuminuria (albumin excretion rate < 30 micrograms/min), two series of patients with microalbuminuria (n = 30 and n = 136), and two series with overt proteinuria (n = 41 and n = 98). Allele 235T frequency was higher among cases with microalbuminuria (0.41 in the two series combined) or overt proteinuria (0.40) than in the normoalbuminuria group (0.36). However, this difference was not statistically significant with this sample size (chi 2 = 1.2, P = NS with 2 df). Under a recessive model, allele 235T homozygotes had a 1.6-fold risk of developing nephropathy relative to carriers of other genotypes, but this value was not significantly different from 1(95% CI = 0.8 to 3.5). The strength of the association did not improve after stratification by degree of glycemic control. With respect to the hypertension in these IDDM patients, no association with allele 235T was found. Allele 235T frequencies in normotensive and hypertensive individuals were 0.363 and 0.353, respectively, among normoalbuminuric IDDM individuals (chi 2 = 0.01, P = NS) and 0.411 and 0.414 among microalbuminuric IDDM subjects (chi 2 = 0.0, P = NS). We conclude that the angiotensinogen polymorphism M235T might influence susceptibility to nephropathy in insulin-dependent diabetes, but its effect, if any, is rather small and independent of hypertension.     

Hydroperoxides in plasma are reduced by intensified insulin treatment. A randomized controlled study of IDDM patients with microalbuminuria

OBJECTIVE: An association between reactive oxygen species and diabetic micro- and macrovascular complications has been proposed. In the present study, we have examined the effect of an improved blood glucose control on plasma levels of hydroperoxides in patients with IDDM. RESEARCH DESIGN AND METHODS: Subjects included 30 young IDDM patients with microalbuminuria who were randomized to receive either continuous subcutaneous insulin infusion (CSII) by a portable insulin pump (n = 15) or conventional insulin treatment (CIT) (n = 15) for 24 months. Plasma levels of hydroperoxides were measured by the ferrous oxidation with Xylenol Orange, version 2 (FOX2) assay. This method measures total lipid hydroperoxides and, unlike other methods, does not suffer from extraction losses. RESULTS: The mean HbA1c level was lower in the CSII group at the end of the study than in the CIT group: (mean [95% CI]) 8.6 (8.1-9.1) vs. 9.6 (9.0-10.3)%, respectively (P < 0.002). The level of plasma hydroperoxides was very similar at the start of the study but was significantly lower in the CSII group compared with the CIT group at the end of the study: 2.9 (2.1-3.7) vs. 4.3 (3.2-5.4) mumol/l, respectively (P < 0.02). In the CSII group, hydroperoxides were reduced by 31% from baseline (P < 0.001), whereas there was no change in levels of hydroperoxides in the CIT group. Mean hydroperoxide levels correlated with mean HbA1c during the study (r = 0.39, P < 0.04). Hydroperoxide levels were associated with the levels of microalbuminuria (r = 0.45, P < 0.02). CONCLUSIONS: This study provides support for the hypothesis that hyperglycemia is an important factor in the generation of hydroperoxides, and, thus, reactive oxygen species, in the circulation of IDDM patients.     

Trienzyme treatment for food folate analysis: optimal pH and incubation time for alpha-amylase and protease treatment

The large interindividual variation in diabetes duration until the onset of nephropathy is partly unexplained. This study was performed to compare renal structure in insulin-dependent (IDDM) patients who had developed signs of nephropathy after a short or long duration of diabetes. Renal biopsies were obtained from 17 IDDM patients, with albumin excretion rate 20-300 microg/min and normal blood pressure. Six patients had <25 years duration ("short-term", early onset of microalbuminuria) and eight patients had duration >30 years ("long-term", late onset of microalbuminuria). Biopsies were obtained 18 months after entry into a study testing the effect of low-dose antihypertensives. Parameters characterizing diabetic glomerulopathy were significantly increased in IDDM patients compared with those in 17 living donors: Basement membrane thickness, mean and (CV): 591 nm (0.17) vs 320 nm (0.12), mesangial volume fraction per glomerulus 0.27 (0.19) vs 0.19 (0.10), matrix volume fraction per glomerulus 0.16 (0.20) vs 0.097 (0.22), matrix star volume 38.5 microm3 (0.43) vs 13.9 microm3 (0.31), (p<10(-4) for each). Comparison of short vs long-term patients showed no significant differences in glomerulopathy parameters, glomerular volume or extracellular material per glomerulus, whereas the fraction of occluded glomeruli was significantly increased in long-term patients. A close correlation obtained between fraction of occluded glomeruli and glomerular filtration rate (r=0.72, p= 0.001). Glomerular occlusion occurred unrelated to the severity of diabetic glomerulopathy. It is suggested that diabetic macroangiopathy and arteriolar hyalinization may play an important role in the renal function of patients with slow development of nephropathy.     

Microalbuminuria is not rare before 5 years of IDDM. EURODIAB IDDM Complications Study Group and the WHO Multinational Study of Vascular Disease in Diabetes Study Group

Microalbuminuria is thought to be rare in people with insulin-dependent diabetes mellitus (IDDM) for less than 5 years. We measured its prevalence in 733 clinic-attending IDDM patients with diabetes duration of 1-5 years in two large multicenter studies [EURODIAB IDDM Complications Study and the World Health Organization (WHO) Multinational Study]. We also compared characteristics of microalbuminuric patients with IDDM for 1-5 years versus more than 5 years' duration. Albumin excretion rate was measured from a timed 24-h urine collection in the EURODIAB Study. Proteinuria was measured by the salicylsulphonic acid test in the WHO Study. The prevalence of microalbuminuria (20-200 micrograms/min, EURODIAB) was 18% [95% confidence interval (CI) 13%-22%)]. The prevalence of light proteinuria was 15% (9%-20%, WHO study). Raised protein excretion was a consistent finding in 34 of the 36 centers. The increased cardiovascular risk (raised blood pressure and total cholesterol) associated with microalbuminuria in patients with IDDM for more than 5 years was also apparent in those with diabetes for 1-5 years. However, repeat urine testing suggested that microalbuminuria before 5 years was more likely to be transient or reversible. In conclusion, these two studies in 36 centers, which used different methods more than 10 years apart, show consistently that raised urinary albumin excretion occurs before 5 years of IDDM. The clinical significance of this needs to be examined by prospective observation.     

Reduction of renal functional reserve in kidney transplant recipients: a possible role of arachidonic acid metabolism alterations

AIM: Renal functional reserve (RFR), resulting from an increase in glomerular filtration (GFR) after protein load, is a matter of debate. In kidney transplant recipients most studies have failed to show conclusive results, reporting either the absence, the reduction or the presence of renal reserve in normo-functioning kidneys. The aim of this study was to investigate RFR in kidney transplant patients as well as the possible hormonal vasoactive alterations underlying the reduction of renal reserve reported in some patients. PATIENTS AND METHODS: We studied 8 controls and 25 patients, the latter with no history of acute rejection for at least 12 months and GFR >50 ml/min. The 25 patients were divided into 2 groups based on the presence (10) or the absence (15) of RFR. RESULTS: Both the RFR group and the controls experienced a similar increase of GFR after oral protein load: 24.3 +/- 15.57% vs 24.4 +/- 10.8%. The group without RFR showed a paradoxical reduction of GFR after oral protein load: 13.3 +/- 13.2% (p <0.001). We analyzed the filtration fraction (FF) and observed that the group without RFR had higher values than the group with RFR and the controls: 0.35 +/- 0.11 vs 0.29 +/- 0.07 (p = 0.01) and vs 0.26 +/- 0.02 (p = 0.04). The hyperfiltration state observed in the group without RFR was sustained by a high level of thromboxane. The urine ratio TxB2/6ketoPgF1alpha was higher in the group without RFR than in the RFR group 0.78 +/- 0.2 vs 0.64 +/- 0.1 (p = 0.01). This ratio decreased only in the RFR group after a meat meal. In all the patients, changes of TxB2/6ketoPGF1alpha were inversely correlated to changes of GFR after a meat meal (r = -0.6, p = 0.01). CONCLUSIONS: In conclusion, these data demonstrate that kidney transplant recipients with good organ function can be grouped according to the presence of RFR. RFR appears to be inversely correlated with the TxB2/6ketoPGF1alpha ratio, and its decrease seems to be linked to the failure of thromboxane to decrease and prostacycline to increase after a meat meal.     

Effect of changes in daily protein intake on renal function in chronic renal insufficiency: differences in reaction according to disease entity

Protein restriction is advocated in patients with chronic renal insufficiency (CRI) in an attempt to slow down further renal function deterioration, with the most obvious effect in patients with chronic glomerulonephritis (GN) and diabetic nephropathy, and much less in other disease entities, such as adult polycystic kidney disease (APKD), tubulointerstitial nephritis (TIN) and nephrosclerosis (NS). The mechanism by which protein restriction slows down the progression of renal failure remains unclear. Decline of hyperfiltration has been implicated. Whether long-term protein restriction in patients with CRI is associated with a decrease in hyperfiltration is not clear. We studied the effects of prolonged protein intake variation (isocaloric diets in 4-week periods of low (goal: 30-40 g protein daily) and high protein intake (goal: 80-90 g daily) on renal function in 51 patients with CRI. Patients were divided into subgroups according to the underlying renal disease (GN, n = 17; APKD, n = 9; TIN, n = 12; NS, n = 13). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured at the end of each study period. Overall, GFR rose from 39 (9-90) to 46 (9-100) ml/min/1.73 m2 (median and ranges, p < 0.01), and ERPF from 158 (39-558) to 171 (32-676) ml/min/1.73 m2 (p < 0.01). GFR rose significantly in GN (15%, range -23 to 51%), APKD (5%, range -10 to 33%), and NS (8%, range -8 to 25%). ERPF only rose significantly in GN (14%, range -45 to 47%) and APKD (9%, range -9 to 25%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal reserve is normal in adults born with unilateral renal agenesis and is not related to hyperfiltration or renal failure

This study was carried out to examine the renal hemodynamic response in adult patients with single kidneys born with unilateral renal agenesis. A group of 21 patients with unilateral renal agenesis were divided into three groups according to their glomerular filtration rate (GFR): 112 +/- 3 ml/min x 1.73 m2 in group A, 68 +/- 3.2 ml/min x 1.73 m2 in group B, and 40.7 +/- 3.3 ml/min x 1.73 m2 in group C. Mean arterial blood pressure was significantly higher in the patients of group C who were also proteinuric. The renal hemodynamic response to an oral protein load (2 g/kg of protein as beefsteak) was normal in all groups and unrelated to hyperfiltration or to renal failure and proteinuria. The study indicates that in patients with renal agenesis, the hemodynamic response to a protein challenge is similar to that of kidney donors, renal transplant recipients and uninephrectomized patients. The paper also demonstrates that the renal response to a protein challenge is inadequate to identify patients with renal agenesis who are at risk of developing renal disease. Finally, in renal agenesis with renal disease, creatinine clearance overestimated the GFR by an average of 32.7%.     

Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy

BACKGROUND: The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study. METHODS: 97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat. FINDINGS: During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy. INTERPRETATION: In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.     

PREPARED: Preparation for Angiography in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocols for cardiac catheterization in mild-to-moderate renal dysfunction

BACKGROUND: IV hydration before and after cardiac catheterization is effective in preventing contrast-associated renal dysfunction for patients with mild-to-moderate renal insufficiency, but necessitates overnight hospital admission. We tested an outpatient oral precatheterization hydration strategy in comparison with overnight IV hydration. METHODS: We randomized 36 patients with renal dysfunction (serum creatinine > or = 1.4 mg/dL) undergoing elective cardiac catheterization to receive either overnight IV hydration (0.45 normal saline solution at 75 mL/h for both 12 h precatheterization and postcatheterization; n = 18) or an outpatient hydration protocol including precatheterization oral hydration (1,000 mL clear liquid over 10 h) followed by 6 h of IV hydration (0.45 normal saline solution at 300 mL/h) beginning just before contrast exposure. The predefined primary end point was the maximal change in creatinine up to 48 h after cardiac catheterization. RESULTS: The inpatient and outpatient groups were well matched for baseline characteristics and contrast volume. By protocol design, the outpatient group received a greater volume of hydration, although the net volume changes were comparable in the two groups. The maximal changes in serum creatinine in the inpatient (0.21+/-0.38 mg/dL; 95% confidence interval [CI], 0.02 to 0.39 mg/dL) and outpatient groups (0.12+/-0.23 mg/dL; 95% CI, 0.01 to 0.24 mg/dL) were comparable (p = not significant). There were no instances of protocol intolerance. CONCLUSIONS: A hydration strategy compatible with outpatient cardiac catheterization is comparable to precatheterization and postcatheterization IV hydration in preventing contrast-associated changes in serum creatinine. Hospital admission for IV hydration is unnecessary before elective cardiac catheterization in the setting of mild-to-moderate renal dysfunction.     

The functional anatomy of imagining and perceiving colour

OBJECTIVE: To determine whether the progression of urinary albumin excretion rate (AER) is higher during puberty than before or after this period. RESEARCH DESIGN AND METHODS: A prospective study was conducted in which normoalbuminuric prepubertal (n = 20), pubertal (n = 28), and postpubertal (n = 26) IDDM groups matched for diabetes duration and long-term metabolic control were followed for 3 years. At 6-month intervals, 24-h urine collection was used to determine AER. RESULTS: AER increased significantly over a period of 3 years in the pubertal (P = 0.001) and postpubertal (P = 0.003) subjects but not in prepubertal subjects. The annual progression of AER was significantly higher in the pubertal group than in the prepubertal (P = 0.001) or postpubertal (P = 0.001) groups. Six pubertal, two postpubertal, and none of the prepubertal subjects developed microalbuminuria (AER > or = 20 micrograms/min on two consecutive occasions) over a 3-year period (P = 0.047). Multiple logistic regression analysis showed that the risk of development of microalbuminuria was increased in pubertal subjects compared with the prepubertal and postpubertal subjects (adjusted relative risk [95% CI]: 4.3 [1.5-9.3], P = 0.012, and 2.1 [1.1-5.0], P = 0.023, respectively). CONCLUSIONS: Puberty represents an independent risk of the development of microalbuminuria in diabetes. This findings suggests that the endocrine changes of puberty lead to an accelerated process of early kidney damage in diabetes. In pediatric diabetes care, screening for microalbuminuria is needed soon after the onset of puberty.     

Dopamine D2 receptors mediate glomerular hyperfiltration due to amino acids

Renal dopamine has been proposed to be involved in the regulation of glomerular filtration rate (GFR). Because inhibition of dopamine D2 receptors abolishes the renal hyperfiltration due to amino acid load, we tested the hypothesis that pharmacological activation of D2-like receptors mimicked this renal response. In anesthetized rats, quinpirole (0.3 microgram . 100 g-1 . min-1), an agonist for receptors of the D2-like family, caused an increase in GFR by 20 +/- 2%, which corresponded to that provoked by infusion of an 10% amino acid solution. The D2 receptor antagonist S(-)-sulpiride that acts both centrally and peripherally completely abolished the renal hemodynamic response to quinpirole and to amino acids whereas domperidone, a peripherally acting D2 receptor antagonist, inhibited this hyperfiltration only in part. Urinary dopamine excretion increased in response to amino acid infusion whether GFR increased or not. We conclude that, in anesthetized rats, dopamine D2 receptors contribute to the amino acid-induced hyperfiltration and that both central and peripheral receptors might be involved, whereas dopamine excreted into the urine does not appear to play a functional role in this renal hemodynamic response.     

Modulation of renal kallikrein production by dietary protein in streptozotocin-induced diabetic rats

Renal kallikrein levels and excretion rates are increased in insulin-treated diabetic rats with hyperfiltration, and inhibition of kallikrein or blockade of kinin receptors reduces GFR and RPF. In contrast, insulin-deprived severely (SD) diabetic rats that display renal vasoconstriction show reduced levels and excretion rates of renal kallikrein. In these two models, dietary protein manipulation was utilized to study further the relationships between renal kallikrein and renal hemodynamic regulation. Insulin-deprived SD and insulin-treated moderately diabetic (MD) rats were fed a low (9%), normal (25%), and a high (50%) protein diet. In SD rats fed the 50% protein diet, GFR, RPF, and kallikrein excretion rate were increased compared with SD rats fed the 25% protein diet (GFR, 2.66 +/- 0.16 versus 1.74 +/- 0.30 mL/min; RPF, 7.78 +/- 0.58 versus 5.14 +/- 1.03 mL/min; total kallikrein, 248 +/- 24 versus 120 +/- 30 micrograms/24 h, SD 50% versus SD 25%, respectively; P < 0.005). In MD rats fed the 9% protein diet, GFR, RPF, and kallikrein excretion rate were significantly reduced compared with MD 25% protein-fed rats (GFR, 1.54 +/- 0.07 versus 1.95 +/- 0.09 mL/min; RPF, 5.58 +/- 0.35 versus 7.81 +/- 0.35 mL/min; total kallikrein, 119 +/- 8.3 versus 219 +/- 15 micrograms/24 h, MD 9% versus MD 25%, respectively; P < 0.005). Protein restriction in normal nondiabetic rats resulted in a twofold decrease in kallikrein mRNA levels. These findings suggest that the renal hemodynamic response to dietary protein manipulation in diabetic rats could be mediated via changes in renal kallikrein-kinin system activity.     

Urinary albumin excretion rate and glomerular filtration rate in single-kidney type 2 diabetic patients

OBJECTIVE: To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN). RESEARCH DESIGN AND METHODS: Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 +/- 9 years; diabetes duration 8.5 +/- 7 years), 17 SKN (2 men, age 57 +/- 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method. RESULTS: SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 microg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 microg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 +/- 21.4 ml x min(-1) x 1.73 m(-2)) and SKD patients (73.0 +/- 21.5 ml x min(-1) x 1.73 m(-2)) were similar but higher than the one-kidney GFR (GFR / 2) of the age-, sex-, and BMI-matched normal individuals (50.5 +/- 9.0 ml x min(-1) x 1.73 m(-2)) and normoalbuminuric type 2 diabetic patients (54.0 +/- 11.6 ml x min(-1) x 1.73 m(-2)). CONCLUSIONS: Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.     

Perinatal transport casebook. Maternal transport: a protocol for ambulance transfer from rural to regional facility

BACKGROUND: Renal functional reserve is the normal increase in renal blood flow after a protein load, and reduced or absent renal functional reserve is an early index of renal impairment. Renal blood flow is frequently reduced during acute oedematous exacerbations of chronic obstructive pulmonary disease (COPD). It is possible that patients with severe COPD in the stable state may have a reduced or absent renal functional reserve which could be a factor in oedema formation. METHODS: Sixteen stable patients with severe COPD and five normal controls were studied. The mean (SD) arterial oxygen and carbon dioxide tensions (PaO2, PaCO2) and forced expiratory volume in one second (FEV1) of patients with COPD were 8.1 (1.04) kPa, 6.3 (0.69) kPa, and 0.74 (0.27) 1, respectively. The pulsatility index (PI), an index of renovascular resistance, was measured non-invasively by Doppler ultrasonography at baseline and at intervals after a protein load of 250 g steak. RESULTS: The PI fell after the protein load in the normal subjects from 1.04 (0.19) to 0.84 (0.17), mean difference 0.20, 95% confidence interval of difference (CI) 0.14 to 0.27, p < 0.001. In the COPD group there was no change; baseline PI = 1.04 (0.16), PI after protein load = 1.08 (0.19), mean difference = -0.04, 95% CI-0.11 to 0.04, p = NS. Six of the patients with COPD were normocapnic and 10 were hypercapnic (PaCO2 > or = 6.0 kPa). The normocapnic patients had no significant change in PI (baseline PI = 1.07 (0.15), PI after protein load = 1.01 (0.16), mean difference = 0.06, 95% CI -0.03 to 0.15) while in the hypercapnic patients the PI tended to rise (baseline PI = 1.03 (0.17), PI after protein load = 1.12 (0.21), mean difference = -0.09, 95% CI 0.18 to 0.007, p = 0.06). CONCLUSIONS: Renal haemodynamics were unchanged after a protein load in patients with severe COPD, suggesting that they had no renal functional reserve. This may be a factor in the development of oedema frequently seen in patients with severe COPD, particularly in hypercapnic patients.     

Randomised multicentre study of a low-protein diet on the progression of chronic renal failure in children. European Study Group of Nutritional Treatment of Chronic Renal Failure in Childhood

BACKGROUND: Some studies have suggested that a low-protein diet slows the deterioration of renal function in patients with chronic renal failure (CRF). The effects of a low-protein diet on renal function and growth, have not been assessed in a large, prospective randomised trial in children with CRF. METHODS: A 2-year prospective, stratified, and randomised multicentre study recruited 191 patients aged 2-18 years. After a run-in period of at least 6 months, patients were stratified into either a progressive or non-progressive category based on the change in creatinine clearance in this period. The patients were also stratified into three renal-disease categories and then randomly assigned to a control or diet group. In the diet group, the protein intake was the lowest, safe WHO recommendation--i.e., 0.8-1.1 g/kg daily adjusted for age. All patients were advised to have a calorie intake of at least 70% of the WHO recommendations. Glomerular filtration rate (GFR) was measured every 2 months by creatinine clearance; dietary compliance was checked by urinary urea-nitrogen excretion and dietary diaries (weighing method). 112 patients completed an optional third year of the study. FINDINGS: The low-protein diet did not affect growth. However, there was no effect of diet on the mean decline in creatinine clearance over 2 years (diet vs control: progressive group -9.7 [SD 8.0] vs -10.7 [11.8] mL/min per 1.73 m2; non-progressive group -2.5 [7.5] vs -4.3 [10.0] mL/min per 1.73 m2). Patients classified as having progressive disease were older and had a lower creatinine clearance and a higher blood pressure at randomisation, and had a greater decrease in creatinine clearance than non-progressive patients. On multivariate regression analysis proteinuria (partial R2 = 0.259) and systolic blood pressure (partial R2 = 0.087) were independent predictors of the change in GFR. Similar results were found after the study was extended for a third year. INTERPRETATION: A low-protein diet for 3 years did not affect the decrease in renal function in children with CRF. Proteinuria and blood pressure explain a large part of the variability of, and may be causally related to the decline in the GFR.