Increased renal gene transcription of protein kinase C-beta in human diabetic nephropathy: relationship to long-term glycaemic control.

AIMS/HYPOTHESIS: Activation of protein kinase C (PKC) isoforms has been implicated as a central mediator in the pathogenesis of diabetic nephropathy. Although high glucose levels stimulate catalytic activity of PKC, the effects of high glucose levels on the expression of genes encoding PKC isoforms are unknown. We sought to determine whether in addition to activation, diabetes may lead to increased transcription of two PKC isoforms that have been implicated in the pathogenesis of diabetic nephropathy, PKC-alpha and PKC-beta. METHODS: Recent advances in molecular biological techniques now permit quantitative analysis of mRNA from archival, formalin-fixed, paraffin-embedded tissue sections. RNA was extracted from scraped 6 microm sections of biopsy tissue, and PRKC-alpha and PRKC-beta (also known as PRKCA and PRKCB) mRNA measured using real-time PCR. Expression of genes encoding PKC isoforms was examined in renal biopsies (n=25) with classical histological features of diabetic nephropathy and compared with that in normal control tissue (n=6). Peptide localisation of PKC-alpha, PKC-beta and the activated forms phosphorylated PKC-alpha and -beta was also performed on matched paraffin-embedded sections of renal biopsies using immunohistochemistry. The effects of high glucose on PRKC-beta expression and peptide production in cultured human proximal tubular epithelial cells were assessed. RESULTS: Quantitative real-time PCR demonstrated a 9.9-fold increase in PRKC-beta mRNA in kidney biopsies of diabetic patients relative to control (p<0.001). No increase in PRKC-alpha expression was seen. In addition, a correlation between renal PRKC-beta mRNA and HbA(1c) was observed in diabetic patients (r=0.63, p<0.05). There was co-localisation of PKC-beta and phospho-PKC-beta predominantly to proximal tubules. A 60% increase in PRKC-beta mRNA and peptide in cultured human proximal tubular epithelial cells exposed to high glucose (p<0.05) was seen in vitro. CONCLUSIONS/INTERPRETATION: PKC-beta is upregulated at the gene expression level in human diabetic nephropathy. PRKC-beta mRNA correlates closely with serum HbA(1c), possibly partially explaining the relationship between glycaemic control and progression of diabetic nephropathy. Archival human tissue provides a valuable resource for molecular analyses.

Remission of nephrotic-range albuminuria reduces risk of end-stage renal disease and improves survival in type 2 diabetic patients.

AIMS/HYPOTHESIS: We evaluated the impact of remission of nephrotic-range albuminuria (>2500 mg/24 h) (NRA) on end-stage renal disease (ESRD) and mortality in type 2 diabetic patients with nephropathy. METHODS: This was a follow-up observational study involving all 79 patients (35%; 62 men, 17 women) with NRA from a cohort of type 2 diabetic patients with nephropathy that was followed for at least 3 years at the Steno Diabetes Center (n=227). Patients were followed from the onset of NRA until death or January 2005. The mean age (+/-SD) was 60+/-8 years and known diabetes duration was 14+/-7 years. Remission of NRA was defined as sustained albuminuria <600 mg/24 h for at least 1 year. RESULTS: The duration of follow-up after onset of NRA was 6.5 years (range 2-20 years). Remission was induced in 20 (25%) of the patients, all treated with ACE inhibitors or angiotensin-II receptor blockers. Remission lasted 4.1 years (range 1-10 years) and only three patients relapsed. At the end of follow-up, only 30% (two ESRD and four deaths) of the 20 patients with remission had reached the composite endpoint of ESRD or death, in contrast to 66% (16 ESRD and 23 deaths) of the 59 patients without remission (p<0.01). Cox regression analysis revealed that remission was associated with a risk reduction of 67% (95% CI 10-87) for reaching the composite endpoint of ESRD or death and of 69% (95% CI 21-88%) for death alone. Male sex, greater age and systolic blood pressure at onset of NRA were also independently associated with an increased risk of ESRD and death. CONCLUSIONS/INTERPRETATION: Aggressive antihypertensive treatment can lead to long-term remission of NRA in a sizeable proportion of patients with type 2 diabetes. Such remission is associated with a slower progression of nephropathy and substantially improved survival.

Renal function and structure in albuminuric type 2 diabetic patients without retinopathy.

BACKGROUND: In type 2 diabetic patients without retinopathy the cause of albuminuria is heterogeneous and our knowledge of the relationship between kidney structure and function in these patients is limited. Therefore, a long-term study evaluating the structural-functional relationship in albuminuric type 2 diabetic patients without retinopathy was performed. METHODS: Mesangial volume of total glomerular volume (Vv (mes/glom)), fractional area of focal interstitial fibrosis and tubular atrophy of cortical area (FF) and percentage of sclerosed glomeruli (S/G) were measured on kidney biopsies from 49 type 2 diabetic patients without retinopathy. Glomerular filtration rate (GFR) was determined at least 3 times (median 8 (range 3-20)) in each patient. Patients were followed for 7.0 (1.1-17) years. Albuminuria and blood pressure were measured every 3-6 months. RESULTS: Biopsies revealed diabetic glomerulopathy (DG-group) in 69% of the patients (27 male/7 female) and normal glomerular structure (n=9) or glomerulonephritis (n=6) were found in 31% (13 male/2 female) (NDG-group). In the DG-group GFR decreased from 97+/-5 to 66+/-5 ml/min/1.73 m(2) (mean+/-SE) (P<0.001), with a rate of decline in GFR of 5.3+/-0.8 ml/min/year and in the NDG-group from 93+/-7 to 74+/-11 ml/min/1.73 m(2) (P<0.01), with a rate of decline in GFR of 3.2+/-0.9 ml/min/year, P=0.09 between groups. Mean arterial blood pressure decreased from 109+/-2 to 100+/-2 mm Hg (P<0.001) (DG-group) and remained unchanged in the NDG-group. An association between Vv (mes/glom) and rate of decline in GFR was revealed mainly in the NDG-group (DG-group; r=0.31, P=0.07 and NDG-group; r=0.74, P<0.01). Furthermore, the rate of decline in GFR seemed to be associated with FF in the NDG group (r=0.48, P=0.07). Percentage of S/G was not associated with the rate of decline in GFR. Vv (mes/glom) was associated with mean albuminuria during follow-up in the DG group; r=0.38, P<0.03 (NDG group; r=0.51, P=0.09). Albuminuria was an independent predictor of the rate of decline in GFR in both groups (DG-group; r=0.40, P<0.05 and NDG-group; r=0.61, P<0.01). CONCLUSIONS: Our study revealed a tendency to a faster rate of decline in GFR in the DG-group compared to the much smaller NDG-group, characterized by marked heterogeneity of the underlying kidney lesions and rate of GFR loss. A large mesangial volume fraction was associated with increased albuminuria and loss in GFR. Albuminuria acted as a progression promoter in both groups.

Autoregulated glomerular filtration rate during candesartan treatment in hypertensive type 2 diabetic patients.

BACKGROUND: Impaired autoregulation of the glomerular filtration rate (GFR) implies disturbances in the downstream transmission of the systemic blood pressure into the glomerulus, leading to capillary hypertension or hypotension dependent of the level of blood pressure. The impact on renal autoregulation of different antihypertensive drugs in animals has been elucidated, whereas information in humans is lacking. METHODS: A randomized, double-blind crossover study with candesartan cilexetil 16 mg o.d. and placebo was performed in 17 hypertensive type 2 diabetic patients without nephropathy. Each treatment arm lasted four weeks. On the last day, GFR (single shot [51Cr] EDTA plasma clearance technique for 4 hours) was measured twice between 8 a.m. and 5 p.m., first without clonidine and then after an intravenous injection of clonidine 75 microg. Blood pressure (Takeda TM2420, A&D, Tokyo, Japan) was measured every ten minutes, and the urinary albumin excretion rate (UAER) was measured by ELISA during each GFR determination. RESULTS: Candesartan induced a mean (SE) reduction in mean arterial blood pressure (MABP) of 6 (2) mm Hg (P < 0.02) and had a tendency to reduce UAER (P = 0.07), while GFR remained unchanged (95 vs. 93 mL/min/1.73 m2). Clonidine reduced MABP with 17 (2) versus 16 (1) mm Hg during placebo versus candesartan 16 mg o.d., respectively (NS). GFR diminished in average from 95 (3) to 92 (4) mL/min/1.73 m2 with placebo (NS), and from 93 (3) to 89 (4) mL/min/1.73 m2 during treatment with candesartan (NS). The mean difference (95% CI) in the changes in GFR between the examination with placebo and with candesartan was 0.1 (-5.5 to 5.8) mL/min/1.73 m2 (NS). CONCLUSION: Candesartan reduces blood pressure without adversely altering the preserved ability to autoregulate GFR in hypertensive type 2 diabetic patients without nephropathy.

The impact of glycaemic control on autoregulation of glomerular filtration rate in patients with non-insulin dependent diabetes.

UNLABELLED: The ability of the kidney to maintain constancy of glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in patients with diabetic and non-diabetic nephropathy and in streptozotocin diabetic rats during hyperglycaemia. Information on the potential impact of acute changes in glycaemic control on autoregulation of GFR in diabetic patients is lacking. Therefore the aim of our study was to evaluate the effect of acute lowering of blood pressure (BP) on GFR during normoglycaemia and hyperglycaemia. We investigated 14 (12m/2f) normoalbuminuric patients with non-insulin dependent diabetes (NIDDM). The patients were examined in random order on two separate days with blood glucose (BG)<10 mmol/L or with BG>15 mmol/L. GFR (single shot [51Cr] EDTA plasma clearance technique) was measured twice each day; first without clonidine (baseline) followed by intravenous injection of clonidine 100-150 microg. We measured BG (One Touch 2), and BP (Takeda TM2420) several times during each GFR measurement. Clonidine reduced mean arterial blood pressure with 20 (1.4) vs. 16 (1.2) mmHg (mean (SE)) with BG<10mmol/L and with BG>15 mmol/L, respectively (p=0.053). GFR diminished in average from 92 (3.1) to 86 (3.7) ml/min/1.73m2 with BG<10 mmol/L (p<0.05), and from 102 (4.1) to 98 (4.2) ml/min/1.73 m2 with BG> 15 mmol/L, NS. Mean difference between changes in GFR (95% confidence interval) between the examination with BG<10 mmol/L and with BG>15 mmol/L were 2.3 (-1.3 to 5.9) ml/min/1.73 m2 (NS). The mean BG during normoglycaemia was 6.9 (0.3) vs.16.9 (0.4) during hyperglycaemia. CONCLUSION: Our study suggests that acute changes in glycaemic control have no detectable effect on autoregulation of GFR in NIDDM patients. Hyperglycaemia enhances GFR.

Causes of albuminuria in patients with type 2 diabetes without diabetic retinopathy.

BACKGROUND: The causes of albuminuria in patients with type 2 diabetes are heterogeneous and are scantily investigated, particularly if the patient has a lack of diabetic retinopathy. Therefore, we evaluated the structural background of albuminuria in a large consecutive group of Caucasian patients with type 2 diabetes without retinopathy. METHODS: Three hundred forty-seven consecutive patients with type 2 diabetes with persistent albuminuria (>300 mg/24 h) were recorded. Fundus photo (80%) and ophthalmoscopy were performed. Ninety-three (27%) had no retinopathy, and a kidney biopsy was performed in 52 (56%) of these patients. An insufficient tissue sample was obtained in one patient. The biopsies were evaluated by three masked nephropathologists. RESULTS: The biopsies revealed diabetic glomerulopathy in 69% of the patients (28 males and 7 females), while the remaining 31% (95% CI, 18 to 44) had either nondiabetic glomerulopathies such as glomerulonephritis (N = 7, 6 males and 1 female, 13%) or normal glomerular structure (N = 9, 7 males and 2 females, 18%). No significant differences in sex, age (56 +/- 8 vs. 53 +/- 10 years, mean SD), body mass index (30 +/- 4 vs. 31 +/- 8 kg/m2), known duration of diabetes (6 +/- 6 vs. 4 +/- 3 years), GFR (95 +/- 29 vs. 89 +/- 31 mL/min/1.73 m2), albuminuria (1304 +/- 169 to 4731 vs. 1050 +/- 181 to 5176 mg/24 hours), blood pressure (150/87 +/- 16/9 vs. 145/89 +/- 16/9 mm Hg), prevalence of hypertension (89 vs. 100%), hemoglobin A1c (8.2 +/- 1.6% vs. 9.0 +/- 2.5%), and serum total cholesterol (7.1 +/- 2.4 vs. 6.3 +/- 1.6 mmol/L) were found between patients with and without diabetic glomerulopathy. CONCLUSIONS: Albuminuric patients with type 2 diabetes without diabetic retinopathy have a prevalence of biopsies with normal glomerular structure or nondiabetic kidney diseases of approximately 30%. A separation between diabetic and nondiabetic glomerular lesions was not possible based on demographic, clinical, or laboratory data. Consequently, such patients may require further evaluation, including a kidney biopsy.

QTc interval length and QT dispersion as predictors of mortality in patients with non-insulin-dependent diabetes.

Patients with non-insulin-dependent diabetes (NIDDM) are at independent risk of cardiovascular death. The reason is only partially understood. The aim of our study was therefore to evaluate the impact of corrected QT interval length (QTc) and QT dispersion (QT-disp) on mortality in a cohort of 324 Caucasian NIDDM patients. A resting 12-lead ECG was recorded at baseline. Maximum (QT-max) and minimum QT (QT-min) intervals were measured, and QT-max was corrected for heart rate (QTc-max). QT-disp was defined as the difference between QT-max and QT-min. QTc-max was 454 (376-671) ms(1/2) (median (range)) and QT-disp 61 (0-240) ms. Prolonged QTc interval (PQTc), defined as QTc-max > 440 ms(1/2), was present in 67% of the patients and prolonged QT-disp (PQT-disp), defined as QT-disp > 50 ms, was present in 51%. During the 9-year follow-up period, 100 patients died (52 from cardiovascular diseases). Thirty-seven percent of the patients with PQTc died compared with 17% with normal QTc interval (p<0.001). The Cox proportional hazard model, including putative risk factors at baseline, revealed the following independent predictors of all cause mortality; QTc-max (p<0.05), age (p<0.0001), albuminuria (p<0.01), retinopathy (p<0.01), HbA1c (p<0.05), insulin treatment (p<0.01), total cholesterol (p<0.01), serum creatinine (p<0.05) and presence of cardiac heart disease based on Minnesota coded ECG (p<0.001). Whereas QT-disp was not a predictor, QTc-max interval was an independent predictor of cardiovascular mortality. Our study showed a high prevalence of QTc and QT-disp abnormalities and indicated that QTc-max but not QT-disp is an independent predictor of all cause and cardiovascular mortality in NIDDM patients.

Course of glomerular filtration rate in albuminuric type 2 diabetic patients with or without diabetic glomerulopathy.

OBJECTIVE: To evaluate and compare the clinical course and prognosis in type 2 diabetic patients with persistent albuminuria, with biopsy-proven diabetic glomerulosclerosis (DG), or with nondiabetic glomerulopathies (NDG). RESEARCH DESIGN AND METHODS: A kidney biopsy was performed in 34 consecutive type 2 diabetic patients with persistent albuminuria (> or = 300 mg/24 h). Glomerular filtration rate (GFR) (51Cr-EDTA) was determined at least once a year, and albuminuria, arterial blood pressure, and HbA1c were determined every 3-6 months. RESULTS: The biopsy revealed DG in 26 patients (25 men/1 woman) (DG group), age 52 +/- 2 (mean +/- SEM) years, and NDG in 8 patients (7 men/1 woman) (NDG group), age 54 +/- 3 years. The patients were followed for a median of 7.7 years (range 1.0-14.2). In the DG group, GFR decreased from 82 (24-146) to 38 (2-116) ml.min-1.1.73 m-2 (P < 0.001), with a median rate of decline in GFR of 5.6 (0.3-21.6) ml.min-1.year-1, and in the NDG group, GFR decreased from 107 (89-135) to 90 (17-119) ml.min-1.1.73 m-2 (P < 0.05), with a median rate of decline in GFR of 1.3 (0.3-7.6) ml.min-1.year-1 (P < 0.05 between groups). In the DG group, albuminuria increased from 1.4 (0.3-7.2) to 2.6 (0.1-21.6) g/24 h (P < 0.05) and in the NDG group, decreased from 2.2 (0.8-8.7) to 0.8 (0.2-2.5) g/24 h (P = 0.05). Mean arterial blood pressure (MABP) decreased from 118 +/- 3 to 104 +/- 3 mmHg (P < 0.05) in the DG group, whereas it remained unchanged in the NDG group (106 +/- 3 vs. 105 +/- 3 mmHg). In the DG group, the rate of decline in GFR correlated with systolic blood pressure (r = 0.62, P < 0.001), MABP (r = 0.52, P < 0.01), albuminuria (r = 0.55, P < 0.005), and GFR at entry (r = -0.45, P < 0.05). CONCLUSIONS: Our study demonstrated a more rapid decline in GFR and a progressive rise in albuminuria in type 2 diabetic patients with DG compared with type 2 diabetic patients with NDG.

Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathies.

BACKGROUND: The ability of the kidney to maintain constancy of the glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in diabetic nephropathy. Whether this is also the case in patients with nondiabetic nephropathies is not known. METHODS: We investigated the effect of acute lowering of blood pressure (BP) on GFR in 16 (8 males and 8 females) albuminuric subjects suffering from different nondiabetic nephropathies and in 14 (7 males and 7 females) controls matched with respect to sex, age, BP, and baseline GFR. The subjects received in random order an intravenous injection of either clonidine (150 to 225 microg) or saline (0.154 mmol/liter) within two weeks. We measured GFR ([51Cr]-EDTA), albuminuria (enzyme-linked immunosorbent assay; ELISA), and BP (Takeda TM-2420). RESULTS: Clonidine induced similar reductions in mean arterial BP 17 (2) versus 19 (2) mm Hg [mean (SE)] in patients with nephropathy and in controls, respectively. GFR diminished in average from 89 (6) to 82 (5) ml/min/1.73 m2 (P < 0.05), and albuminuria declined from a geometric mean of 1218 (antilog SE 1.3) microg/min to 925 (1.3) in the patients with nondiabetic nephropathies (P < 0.05), whereas these variables remained unchanged in the control group. The mean difference between changes in GFR (95% confidence interval) between the nondiabetic macroalbuminuric and control subjects was 6.1 (-0.03 to 12.21) ml/min/1.73 m2 (P = 0.051). CONCLUSION: Our study suggests that albuminuric patients with nondiabetic nephropathies frequently suffer from impaired autoregulation of GFR.

Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy.

AIMS: To determine the natural course of kidney function and to evaluate the impact of putative progression promoters in Caucasian Type 2 diabetes mellitus (DM) patients with diabetic nephropathy who had never received any antihypertensive treatment. METHODS: A long-term observational study of 13 normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy. Glomerular filtration rate (GFR) was measured approximately every year (51Cr-EDTA plasma clearance technique). Albuminuria, blood pressure (BP) and haemoglobin A1c (HbA1c) was determined 2-4 times per year and serum cholesterol every second year. RESULTS: The patients (12 males/one female), age 56+/-9 (mean +/- SD) years, with a known duration of diabetes of 10+/-6 years, were followed for 55 (24-105) (median (range)) months. GFR decreased from 104 (50-126) to 80 (39-112) ml x min(-1) x 1.73 m(-2) (P = 0.002) with a median rate of decline of 4.5 (-0.4 to 12) ml x min(-1) x year(-1). During follow-up, albuminuria rose from 494 (301-1868) to 908 (108-2169) mg/24 h (P = 0.25), while BP, HbA1c and serum cholesterol remained essentially unchanged. In univariate analysis the rate of decline in GFR did not correlate significantly with neither baseline nor mean values during follow-up of BP, albuminuria, HbA1c and serum cholesterol. CONCLUSIONS: Our study suggests that normotensive to borderline hypertensive Type 2 DM patients with diabetic nephropathy have a rather slow decline in kidney function, but we did not unravel the putative progression promoters responsible for the variation in rate of decline in GFR.

Low-protein diet and kidney function in insulin-dependent diabetic patients with diabetic nephropathy.

BACKGROUND: Initiation of a low-protein diet (LPD) in patients with various nephropathies induces a faster initial and slower subsequent decline in the glomerular filtration rate (GFR). Whether this initial phenomenon is reversible or irreversible remains to be elucidated. METHODS: We performed an eight-week prospective, randomized, controlled study comparing the effect of an LPD with a normal-protein diet (NPD) in 29 insulin-dependent diabetic patients with diabetic nephropathy. At baseline, the patients were randomized to either an LPD (0.6 g.kg-1.24 hr-1, LPD group, N = 14) or their NPD (NPD group, N = 15) for four weeks (phase I). Between weeks 4 and 8, all patients received their NPD (phase II, recovery). Dietary protein intake (g.kg-1.24 hr-1), GFR (51Cr-EDTA, ml.min-1.1.73 m-2), albuminuria (enzyme-linked immunoadsorbent assay, mg.24 hr-1), and arterial blood pressure (Hawksley random zero sphygmomanometer, mm Hg) were measured at baseline and after four- and eight-weeks of follow-up. During the investigation, all patients in the LPD group (N = 12) and in the NPD group (N = 14) received their usual antihypertensive treatment. RESULTS: At baseline, the LPD group and the NPD group were comparable regarding dietary protein intake, GFR, albuminuria, and arterial blood pressure. During phase I, a significant decline in dietary protein intake, GFR, and albuminuria (mean, 95% CI) was observed in the LPD group [0.4 (0.3 to 0.5) g.kg-1.24 hr-1, 8.6 (3.2 to 13.9) ml.min-1.1.73 m-2, and 28.7 (14.0 to 40.9)%, respectively] compared with the NPD group [0.0 (-0.1 to 0.2) g.kg-1.24 hr-1 (P < 0.0001 between diets), 2.5 (-1.8 to 6.8) ml.min-1.1.73 m-2 (P = 0.07 between diets), and 0.0 (-20.1 to 23.5)% (P < 0.05 between diets), respectively]. Conversely, during phase II, a significant increase in dietary protein intake, GFR, and albuminuria [mean, 95% CI; 0.3 (0.2 to 0.5) g.kg-1.24 hr-1, 5.9 (0.8 to 11.1) ml.min-1.1.73 m-2, and 25.0 (4.5 to 49.6)%, respectively] took place in the LPD group compared with the NPD group [0.0 (-0.2 to 0.1) g.kg-1.24 hr-1 (P < 0.0001 between diets), -2.9 (-6.4 to 0.6) ml.min-1.1.73 m-2 (P < 0.01 between diets), and 2.9 (-18.3 to 29.7)% (P = 0.16 between diets), respectively]. Arterial blood pressure was comparable in the two groups of patients during phase I and II. CONCLUSIONS: Dietary protein restriction for four weeks induces a reversible decline in GFR and albuminuria in insulin-dependent diabetic patients with diabetic nephropathy, whereas systemic blood pressure remains unchanged.

Impaired autoregulation of GFR in hypertensive non-insulin dependent diabetic patients.

We investigated the effect of acute lowering of blood pressure (BP) upon glomerular filtration rate (GFR) in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients, 14 with diabetic nephropathy and 12 with normoalbuminuria. The study was performed twice with the subjects receiving an intravenous injection of either clonidine (150 to 225 micrograms) or saline (0.154 mmol/liter). We assessed GFR, albuminuria, and BP. The two groups were well matched with respect to demographic data, baseline GFR and BP. Clonidine induced similar reductions in mean arterial blood pressure 19 (SE +/- 4) and 21 (SE +/- 3) mm Hg in patients with and without nephropathy, respectively. In the nephropathy group GFR diminished in average from 90 (SE +/- 6) to 81 (SE +/- 7) ml/min/1.73 m2 (P = 0.006), fractional clearance of albumin (x 10(-6)) declined from a geometric mean of 219 (antilog SE /divided by 1.3) to 186 (antilog SE /divided by 1.3) (P = 0.04), and four patients had a complete pressure-passive vasculature, defined as delta GFR% = delta MABP%. A significant correlation between relative reductions in MABP and GFR (r = 0.78, P < 0.001) was demonstrated in albuminuric patients. None of the normoalbuminuric patients had a complete pressure-passive vasculature and there were no significant differences in GFR between the two examinations, but five had abnormal autoregulation of GFR. Mean difference between changes in GFR (95% confidence interval) between the nephropathic and normoalbuminuric group was 5.5 (divided by 2.7 to 13.7) ml/min/1.73 m2 (P = 0.18). Our study suggests that hypertensive NIDDM patients, particularly patients with nephropathy, frequently suffer from impaired or abolished autoregulation of GFR.

[Compression stockings as prevention of hypotension in Cesarean section during spinal anesthesia]. / Kompressionsstrømper som profylakse mod hypotension ved sectio i spinalanaestesi.

Inflatable splints and wrapping of the legs have been shown to be effective against hypotension during spinal anaesthesia for Caesarean section. The aim of this study was to investigate if compression stockings could have a similar effect. Thirty healthy mothers scheduled for elective Caesarean section were randomised to have either compression stockings or no stockings on before spinal anaesthesia. The stockings had a pressure effect of 54 mmHg. The women were preloaded with 20 ml isotonic NaCl one hour preoperatively. Hypotension was defined as either a decrease in systolic blood pressure to 80% of preoperative values or systolic blood pressure under 100 mmHg. Blood pressure was measured every second minute, and ephedrine 5 mg was given in the presence of hypotension. Two patients were excluded in the control group. There were no differences in demographic data, extension of blockade, and spinal injection to delivery time. Nine patients in the group with stockings had either no fall in blood pressure or a fall in blood pressure corrected with only 5 mg ephedrine. In the control group the corresponding number was four patients (p < 0.12). Ephedrine dose between zero and 20 minutes and total ephedrine dose was significantly lower in the group with stockings than in the control group (p < 0.038). Five patients in the control group experienced nausea, no patients in the study group had nausea (p < 0.013). In conclusion, compression stockings stabilised the blood pressure during Caesarean section in spinal anaesthesia and led to a significant smaller need for ephedrine.