Rate of decline of GFR and progression of vascular disease in type 2 diabetic patients with diabetic or vascular nephropathy during the last three years before starting dialysis therapy.

BACKGROUND: The progression of chronic renal insufficiency depends on the type of primary renal disease and blood pressure (BP) levels. We investigated the rate of decline of glomerular filtration rate (GFR) during 3 years prior to the start of dialysis therapy in type 2 diabetic patients with diabetic nephropathy (dNP) or vascular nephropathy (vNP). The aim of the study was to determine differences in the progression of renal insufficiency and the prevalence of vascular diseases in the two patient groups. METHODS: In a retrospective study, we investigated type 2 diabetic patients with chronic renal insufficiency who were undergoing regular controls in our outpatient care unit for at least 3 years prior to the start of dialysis. We evaluated only patients who had already died under chronic dialysis therapy, and whose diagnosis of primary renal disease was histologically conformed at autopsy. A total of 40 type 2 diabetic patients were included in the study. Of these, 28 patients had dNP (age 62 +/- 8 years) and 12 had vNP (age 70 +/- 7 years). The following parameters were determined at 3- to 6-month intervals: body weight, BP, HbA1c, serum creatinine (Cr), Cr clearance (Cockroft formula), cholesterol and triglycerides. The prevalence of vascular disease in the two groups was also assessed. RESULTS: The average decrease in Cr clearance was 7.7 +/- 2.4 ml/min/year in patients with dNP and 7.7 +/- 2.1 ml/min/year in those with vNP (NS). During the entire observation period, mean HbA1c values (7.0 +/- 0.8 vs. 6.8 +/- 0.6%), systolic BP (137 +/- 8 vs. 138 +/- 11 mm Hg) and diastolic BP (86 +/- 4 vs. 87 +/- 7 mm Hg), cholesterol and triglycerides did not differ significantly in the two groups. The prevalence of vascular disease 3 years prior to and at the start of dialysis therapy was similar in patients with dNP and vNP. CONCLUSION: The progression of dNP and vNP is similar at least during 3 years before the start of dialysis therapy. Vascular risk factors and the prevalence of vascular diseases were not significantly different in the two patient groups. However, diabetic patients with ESRD secondary to dNP were significantly younger than those with vNP.

Impact of kidney transplantation on glycemic control and cardiovascular risk factors in insulin-treated diabetic patients receiving cyclosporine: a longitudinal study.

BACKGROUND: In insulin-treated patients with diabetes, kidney transplantation (KTP) may influence glycemic control, insulin requirements, as well as vascular risk profiles, but the data are controversial. In 10 selected insulin-treated diabetic patients with normally functioning kidney transplants, receiving cyclosporine for immunosuppression, we evaluated the fasting blood glucose, HbA1c, lipid levels, blood pressure, and insulin-requirement from 1 year before to 1 year after KTP. RESULTS: There were no significant differences in the mean HbA1c levels 6 and 3 months before transplantation (8.3 +/- 1.7 and 8.0 +/- 1.4%, respectively) and 3 and 12 months after transplantation (8.2 +/- 1.6 and 7.9 +/- 1.5%, respectively). The mean fasting blood glucose levels increased only transiently by 7% during the first week after transplantation (not significant). The insulin requirement was approximately the same at 3 and 6 months before (42 +/- 14 and 42 +/- 13 IU/d, respectively) and at 3 and 12 months after transplantation (44 +/- 13 and 41 +/- 13 IU/mL, respectively). Only 1 week after transplantation did the insulin requirement increase transiently by 14% to 48 +/- 14 IU/d (P < .05). The mean levels of cholesterol and triglycerides as well as mean blood pressure were not significantly different before and after transplantation. CONCLUSION: Only immediately after KTP did mean blood glucose and insulin requirement increase. At least 3 months after transplantation, glycemic control and insulin requirements as well as the vascular risk factors were approximately the same as before the procedure.

Recurrent hyperparathyroidism after total parathyroidectomy due to multiple ectopic parathyroid glands in a patient with long-term haemodialysis.

We report the rare case of a recurrent hyperparathyroidism after total parathyreoidectomy due to multiple ectopic glands in a patient on long-term haemodialysis. In a today 47 years old man with membranoproliferative glomerulonephritis intermittent haemodialysis therapy was started in 1975. In 1982 an advanced secondary hyperparathyroidism with a parathormone (PTH) level > 500 pg/l was diagnosed; later on PTH concentration increased to 2,550 pg/ml. In 1987 total parathyroidectomy with parathyroid autograft into the left forearm was performed. After parathyroidectomy the PTH level fell to 150 pg/ml. In 1993 PTH concentration increased again to 1,750 pg/ml. There was no evidence for recurrent parathyroid glands in the neck or forearm. Therefore, we investigated the substernal region by 99mTc-tetrofosmin scintigraphy and magnetic resonance imaging. Both investigations showed evidence for two ectopic parathyroid glands in the anterior mediastinum. In June 1999 in an open thoracic surgical procedure only the greater parathyroid gland in the anterior mediastinum was isolated, but a second gland was detected in the posterior mediastinum. Both parathyroid glands were resected (histologically hyperplastic parathyroid gland tissue). After surgery the PTH level decreased to 340 pg/ml, but later on PTH increased again to > 1,000 pg/ml in January 2001. A control 99mTc-tetrofosmin scan showed evidence for a third ectopic parathyroid gland in the anterior mediastinum. Recurrent secondary hyperparathyroidism can rarely be caused by recurrent ectopic parathyroid glands in the mediastinum.

The incidence of thrombovenous and thromboembolic complications in kidney transplant patients with recurrent glomerulonephritis is dependent on the occurrence of severe proteinuria.

BACKGROUND: Patients with recurrent glomerulonephritis (RG) after kidney transplantation are at high risk for thromboembolic events but it is unclear when the risk begins to increase. PATIENTS AND METHODS: We evaluated the risk for thrombovenous and thromboembolic complications in relation to the occurrence of severe proteinuria (> or = 2 g protein in 24-hour urine) in 15 renal allograft recipients with biopsy-proven RG, who had received 20 allografts RG. The total period of observation was 53 (10-91) months. The post-transplant period before the occurrence of severe proteinuria lasted 18 (1-34) months and the subsequent proteinuric period until the end of the study, 35 (9-85) months. RESULTS: The monthly incidence of thrombovenous and thromboembolic complications was only 1/18 in the first period before and in contrast, 11/35 in the subsequent period after the occurrence of severe proteinuria. The mean urinary protein excretion increased from 0.4 +/- 0.1 g/day immediately after transplantation to 6.1 +/- 4.8 g/day at the end of the study (p < 0.001). During the same period there was a 1.2-fold increase of fibrinogen (from 366 +/- 88 to 442 +/- 120 mg/dl, p < 0.025) and a 1.2-fold decrease of antithrombin III (from 110 +/- 12 to 92 +/- 12%, p < 0.001). All thrombotic complications occurred in 6 patients with 9 grafts; at the end of the study this group showed higher fibrinogen concentrations (454 +/- 155 versus 433 +/- 89 mg/dl, NS) m and lower antithrombin III levels (88 +/- 11 versus 97 +/- 11%, p < 0.05) than the group without thrombotic complications. CONCLUSION: In kidney transplant patients with RG a high risk for thrombovenous and thromboembolic complications can be obs- served after the occurrence of severe proteinuria; this can mainly be explained by high fibrinogen and low antithrombin III levels. Anticoagulation therapy should be started in patients with RG immediately after the occurrence of severe proteinuria.

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

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

[Malacoplakia: a possible complication of poorly controlled diabetes mellitus?]. / Malakoplakie--eine mögliche Komplikation bei Diabetes mellitus mit schlechter Stoffwechsellage?

HISTORY AND ADMISSION FINDINGS: A 47-year-old woman with poorly controlled diabetes mellitus (HbA1C 9.2%, fasting blood glucose > 200 mg/dl) had complained of moderately severe stabbing pain in the left abdomen. On admission there were no abnormal findings on abdominal palpation. INVESTIGATIONS: Abdominal ultrasound and computed tomography (CT) revealed a partly solid partly cystic well-circumscribed space-occupying lesion, about 15 cm in diameter, in the left abdomen, extending from the lower third of the kidney into the pelvis. DIAGNOSIS, TREATMENT AND COURSE: Biopsy of the lesion showed chronic granulating inflammation with foamy histiocytes (Hansemann macrophages) as characteristic substrate of extensive malakoplakia. Despite the size of the lesion it was not excised but long-term treatment with ciprofloxacin undertaken. At the same time, the diabetes was carefully controlled with ordinary insulin. Ten months later there was no longer any evidence of the lesion by ultrasound and CT. CONCLUSIONS: Even extensive malakoplakia can be successfully treated with ciprofloxacin. Poorly controlled diabetes together with a weak immune status (CD4/CD8 < or = 1) may have favoured the occurrence of malakoplakia.

Bilateral nephrectomy: the best, but often overlooked, treatment for refractory hypertension in hemodialysis patients.

Bilateral nephrectomy for treatment of refractory hypertension in chronic hemodialyzed patients has been infrequently carried out. We analyzed the benefits of this operation on blood pressure, clinical state, drug treatment, and quality of life. In 10 hemodialyzed patients with refractory hypertension, systolic (SBP) and diastolic (DBP) blood pressure were measured 1 month before nephrectomy bilateral and 3, 6, 9, and 12 months after. In addition, the use of antihypertensive drugs before and after surgery was evaluated. Four patients had SBP and DBP values characteristic of malignant hypertension. In all 10 patients hypertension responded neither to reduction of plasma volume by ultrafiltration nor to multiple antihypertensive drug therapy. Hypertensive crises were associated with cerebral hemorrhage in two patients, severe encephalopathy with persistent neural dysfunction in one patient, and encephalopathy and diplopia in another. Three months after bilateral nephrectomy blood pressure decreased significantly (P < .005) and was normal in nine patients. In one noncompliant patient with intradialytic body weight increases of nearly 10%, blood pressure was still elevated. Malignant or drug-resistant hypertension with hypertensive crises is an indication for bilateral nephrectomy. The clinical state and quality of life improved in all patients in the present study and antihypertensive treatment is no longer necessary.

Influence of cigarette-smoking on the progression of clinical diabetic nephropathy in type 2 diabetic patients.

Cigarette smoking was known to promote the progression of diabetic nephropathy in patients with type 1 diabetes, but its influence on the course of diabetic nephropathy in patients with type 2 diabetes had not been previously established. In a prospective follow-up study we therefore compared the progression of nephropathy in type 2 diabetic patients with or without tobacco consumption. Initiation of dialysis treatment or death of the patient were the end points of the study. 36 patients with type 2 diabetes complicated with diabetic nephropathy were included in the study, 16 smoked and 20 did not. The main outcome measures were proteinuria, arterial blood pressure, HbAlc, serum-creatinine and creatinine clearance, which were controlled at least every six months. In the smoking diabetic patients the mean (SD) creatinine-clearance decreased from 82 +/- 10 to 10 +/- 6 ml/min/1.73 m2 over a period of 62 +/- 21 months. The rate of decline of the creatinine-clearance was 1.24 +/- 0.34 ml/min/month. In the non-smoking patients the creatinine-clearance decreased from 79 +/- 8 to 9 +/- 3 ml/min/1.73 m2 within 79 +/- 27 months. The rate of decline in the creatinine-clearance was 0.99 +/- 0.35 ml/min/month (p < 0.025). HbAlc, systolic and diastolic blood pressure as well as serum cholesterol and triglycerides were not significantly different in both patient groups. Therefore, we conclude that cigarette smoking promotes the progression of diabetic nephropathy in patients with type 2 diabetes, just as it is known in type 1 diabetic patients.

[Terminal myoglobinuric renal failure in lovastatin therapy with pre-existing chronic renal insufficiency]. / Terminales myoglobinurisches Nierenversagen unter Lovastatintherapie bei präexistenter chronischer Nierenfunktionsstörung.

Atraumatic rhabdomyolysis with consecutive oliguric renal failure occurred in a 67-year-old man with chronic renal insufficiency in the pre-dialysis phase after four years of therapy with lovastatin without complications. Diuresis remained low after normalization of the muscle enzymes, and the patient required chronic hemodialysis. This case report shows that lovastatin-associated rhabdomyolysis with consecutive myoglobinuric renal failure can be seen also after long-standing lovastatin therapy. In pre-existing renal insufficiency this can lead to earlier requirement of chronic dialysis treatment.

Effect of mild dietary protein restriction on urinary protein excretion in patients with renal transplant fibrosis.

In recent studies, it has been demonstrated that strict dietary protein restriction has a beneficial effect on renal transplant patients who show chronic rejection, or transplant fibrosis respectively; however, the protein intake in those investigations usually has been below 0.6 g/kg day, and such a strong restriction may be associated with both a negative nitrogen balance, and low patient compliance. Our study was therefore undertaken to investigate whether the same beneficial effect could be attained with a more moderate dietary protein restriction in renal transplant recipients. In a randomized cross-over study, 14 patients with biopsy-proven transplant fibrosis received a mildly protein restricted diet (0.7 g/kg/day), and a normal protein diet (1.2 g/kg/day) respectively during two 3-week periods. In the patients undergoing moderate protein restriction, a significant reduction in urinary albumin, and total protein excretion, as well as a decrease in albumin/creatinine ratio was observed at the end of the 3-week period when compared to the patients on normal protein diet (p < 0.05). The 51Cr-EDTA-clearance did not differ at the end of each of these dietary periods. In contrast to earlier studies with lower protein intake, the moderate protein restriction in our investigation was not associated with a decrease in serum proteins. In conclusion, a mildly restricted protein intake has also proved effective in significantly reducing the urinary protein excretion in patients with renal transplant fibrosis, yet, without causing decreasing serumprotein-concentrations, which are a sign for a negative nitrogen balance.

[Serum uric acid level in type 1 and type 2 diabetic patients]. / Serum-Harnsäurespiegel bei Typ-1- und Typ-2-Diabetikern.

In 50 type-1 and 50 type-2 diabetic patients serum uric acid levels were measured. Type-1 diabetics showed significantly lower serum uric acid levels in comparison to type-2 diabetics (p < 0.02). This significant difference has been observed in both women (p < 0.001) and men (p < 0.01). Serum uric acid level was lower in type-1 diabetics than in healthy controls but only in diabetic men the difference was statistically significant (p < 0.001). Male type-2 diabetic patients showed serum uric acid levels similar to the controls, but levels were higher in women with type-2 diabetes (p < 0.001). The results of this study show that in type-1 diabetic patients the serum uric acid levels are lower in normal (creatinine clearance > or = 80 ml/min) as well as in slightly decreased (creatinine clearance < 80 ml/min) glomerular filtration rate. But in type-2 diabetic patients the serum uric acid levels were significantly higher when glomerular filtration rate was below 80 ml/min in contrast to normal renal function (p < 0.05).

Abnormal increases in urinary albumin excretion during pregnancy in IDDM women with pre-existing microalbuminuria.

We compared urinary albumin excretion during and after pregnancy in 30 insulin-dependent diabetic (IDDM) women with normoalbuminuria and in 12 IDDM women with microalbuminuria (> 15 micrograms.min-1) prior to conception. There was a 6.7-fold increase in the urinary albumin excretion up until the third trimester in the women with pre-existing microalbuminuria, compared with a 3.8-fold increase in the normoalbuminuric women. In both groups of patients the urinary albumin excretion reached a peak during the third trimester with 492 +/- 404 micrograms.min-1 in the microalbuminuric women vs 43 +/- 36 micrograms.min-1 in the normoalbuminuric women (p < 0.0005). Two women from each of the groups developed eclampsia with diastolic blood pressure over 90 mm Hg, mild or moderate oedema and macroproteinuria. Four of the pregnant women with pre-existing microalbuminuria showed a transient nephrotic syndrome (33.3%) with protein excretion over 3 g in 24-h urine samples during the third trimester. In contrast, this was not observed in any of the normoalbuminuric women (p < 0.05). Within 12 weeks after delivery the urinary albumin excretion rates dropped to the pre-conception values in both patient groups. Renal function remained normal during pregnancy in both of the groups, with a physiological increase in creatinine clearance up until the third trimester (26% increase in the normoalbuminuric women vs 22% in the microalbuminuric women). In conclusion, the effect of pregnancy on the urinary albumin excretion in diabetic women with pre-existing microalbuminuria is an exaggeration of the increase of albuminuria in diabetic women with normoalbuminuria; normalization occurs within 12 weeks after delivery in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Increases in serum lipids during pregnancy in type 1 diabetic women with nephropathy.

During pregnancy women with Type 1 diabetes do not differ from normal women with respect to pregnancy-associated changes in serum lipid levels. However influence of diabetic nephropathy on lipoprotein metabolism in pregnancy has not been described previously. Changes in lipids were compared during and after pregnancy in 10 Type 1 diabetic women without macroproteinuria as well as in 5 diabetic women with macroproteinuria due to diabetic nephropathy. In the pregnant women with macroproteinuria, compared to the diabetic women without macroproteinuria, we observed both significantly higher total and percent increases in serum levels of total cholesterol (97% versus 48%) and of LDL-cholesterol (137% versus 50%), which had risen progressively throughout gestation. The percent increases in serum triglycerides (115% versus 128%) were similar in both patient groups. Metabolic control was improved during pregnancy in both groups of women. Renal function remained normal throughout pregnancy in the diabetic women without nephropathy and worsened during pregnancy in the proteinuric women. The mean protein excretion showed a physiological rise from 0.107 +/- 0.040 g 24 h-1 before pregnancy to 0.336 +/- 0.234 g 24 h-1 in the third trimester in the nonproteinuric women, and an increase from 2.2 +/- 1.0 to 7.1 +/- 1.7 g 24 h-1 during the same period in the women with macroproteinuria. Therefore, it is concluded that the greater increase in serum lipid levels during pregnancy in the women with pre-existing diabetic nephropathy can mainly be explained by the concomitant increase in proteinuria associated with development of the nephrotic syndrome in these patients.

Similar rate of progression in the predialysis phase in type I and type II diabetes mellitus.

Progression of diabetic nephropathy from the stage of macroproteinuria with near-normal renal function until start of dialysis was compared in 16 patients with type I and 16 patients with type II diabetes mellitus. The mean creatinine clearance at the beginning of the study was 89 +/- 13 ml/min/1.73 m2 in patients with type I and 81 +/- 6 ml/min/1.73 m2 in those with type II diabetes. Dialysis was started after a mean interval of 77 (44-133) months, when creatinine clearance had decreased to 8 +/- 2 ml/min/1.73 m2 in type I diabetic patients. The respective figures for type II diabetic patients were 81 (40-124) months and 7 +/- 2 ml/min/1.73 m2. The mean rate of decrease in creatinine clearance was 1.05 +/- 0.45 ml/min/month in type I and 0.91 +/- 0.41 ml/min/month in type II diabetes. The mean rate of decrease was 1.46 +/- 0.30 ml/min/month in type I diabetic patients with a systolic BP > 160 mmHg versus 0.80 +/- 0.42 ml/min/month with < 160 mmHg (P < 0.01). In the type II diabetics the respective figures were 1.38 +/- 0.40 ml/min/month versus 0.78 +/- 0.15 ml/min/month (P < 0.01). During the observation period the prevalence of coronary heart disease increased from 6 to 50% in type I and from 31 to 87% in type II diabetes. In conclusion, the rate of progression of diabetic nephropathy during the predialytic phase is similar in type I and type II diabetes; BP adversely affects the rate of progression to the same extent in both groups.

[Chronic ethylene glycol poisoning]. / Chronische Ethylenglykolvergiftung.

Over a six-week period a 60-year-old patient had several unexplained intoxication-like episodes. He finally had severe abdominal cramps with changes in the level of consciousness and oligoanuric renal failure (creatinine 4.7 mg/dl). The history, marked metabolic acidosis (pH 7.15, HCO3- 2.2 mmol/l, pCO2 6.6 mmHg) as well as raised anion residue (43 mmol/l) and the presence of oxalates in urine suggested poisoning by ethylene glycol contained in antifreeze liquid. Intensive haemodialysis adequately eliminated ethylene glycol and its toxic metabolites (glycol aldehyde, glycolic acid). Renal function returned within 10 days, although the concentrating power of the kidney remained impaired for several weeks because of interstitial nephritis. The intoxication had been caused by a defective heating-pipe system from which the antifreeze had leaked into the hot-water boiler (the patient had habitually prepared hot drinks by using water from the hot-water tap). Gas chromatography demonstrated an ethylene glycol concentration of 21 g per litre of water.