How pregnancy influences renal function in nephropathic type 1 diabetic women depends on their pre-conceptional creatinine clearance.

Pregnancy in type 1 diabetic women with overt nephropathy can lead to a further deterioration in renal function but it is not clear at what level of pre-conceptional GFR the risk for worsening of renal function begins to increase. Therefore we investigated the influence of pregnancy on renal function in 12 women (14 pregnancies) with pre-conceptional macroproteinuria and near-normal creatinine clearance (range 37-93 ml/min/1.73m2). S-creatinine, creatinine clearance (CrCL), HbA1c and blood pressure (BP) were measured before conception, during each trimester (12th and 24th week of gestation and last week before delivery) and three and six months post-partum. In five diabetic women with six pregnancies (group A) there was a physiological increase in CrCl of 36% up until the 24th week of gestation; their pre-conceptional mean CrCl was 80 (range 70-93) ml/min/1.73m2. In seven women with eight pregnancies (group B) CrCl decreased by 16% during the first two trimesters; the mean CrCl before conception was 61 (37-73) ml/min/1.73m2. In the last week before delivery CrCl worsened transiently in three cases in group A and four in group B, due to pre-eclampsia. Three months post-partum the mean CrCl in group A was 78 (70-91) ml/min/1.73m2, approximately the same as before pregnancy. In group B the mean CrCl was 39 (22-68) ml/min/1.73m2 at this same time; this was 36% lower than the pre-conceptional clearance. Mean HbA1c in both groups were approximately the same, but mean BP tended to be higher during pregnancy in group B, especially in the week before delivery (p<0.05). We conclude that in a high percentage of nephropathic diabetic women with significantly low CrCl before conception, renal function worsens during and after pregnancy. Inadequate antihypertensive therapy may contribute to this.

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.

[Transient extra-osseous increase of isotope activity in the bone scintigram in acetolyt-induced hypercalcemia]. / Passagere extraossäre Aktivitätsanreicherung im Knochenszintigramm bei Acetolyt-induzierter Hyperkalzämie.

A 66 year-old man with chronic renal failure developed hypercalcaemia during acetolyte medication. A technetium-99m phosphate bone scan at this time showed extraosseous isotope uptake in the stomach, which disappeared 2 weeks later after normalisation of the serum calcium level. This phenomenon can be interpreted as transient metatastic calcification during hypercalcaemia.

[Congo red-negative light chain disease with intractable diarrhea]. / Kongorotnegative Leichtkettenerkrankung mit intraktablen Durchfällen.

A 56-year-old man was admitted due to chronic diarrhea with progressive weight loss (30 kg within 1 year). All results of medical investigations were normal. The suspected diagnosis of a neuroendocrinological neoplasm could not be established; there was also no evidence for a lymphoma or amyloidosis. Chronic diarrhea and weight loss persisted over the ensuing weeks. Additionally, impairment of renal function and heart insufficiency with consecutive pericardial effusion as well as peripheral facial paralysis and peripheral neuropathy could be observed. Six months after hospital admission, the patient died due to progressive multiple organ failure. Postmortem examination revealed normal bone marrow. Only with additional immunohistochemical investigations of all organs could the diagnosis of a systemic Congo red-negative light chain disease be established.

Perinatal complications and three-year follow up of infants of diabetic mothers with diabetic nephropathy stage IV.

The objective of the study was to evaluate differences in the perinatal complications and in the 3-year follow up of infants of diabetic mothers with and without diabetic nephropathy stage IV. We compared the fetal and maternal complications and the early postpartal development until 3 years after delivery in 10 children of nephropathic diabetic mothers and 30 children of diabetic mothers without nephropathy. The mean (+/-SD) birthweight of the infants of nephropathic women was 2,250 +/- 496 g versus 3,544 +/- 435 g in the women without nephoropathy (p < 0.01). Births were premature in six pregnancies (60%) of the nephrotic women but in none of the women without nephropathy (p < 0.01). Three infants (30%) of the women with nephropathy showed respiratory distress syndrome in contrast to two babies (6%) of the women without nephropathy. Pre-eclampsia or eclampsia occurred in 6 (60%) pregnant women with and in two women (6%) without diabetic nephropathy (p < 0.01). Nephrotic syndrome was observed in 7 nephrotic women (70%) in contrast to none women without nephropathy. Three years postpartum, six of the children (60%) of nephropathic women had a body weight < the 50th percentile but none of the children of the women without nephropathy did so (p < 0.01). In addition, the children of nephropathic mothers started to speak significantly later (15 +/- 3 versus 12 +/- 13 months postpartum, p < 0.05) and had infectious diseases more commonly (60% versus 6%, p < 0.01) than the children of women without nephropathy. It can be concluded that in pregnancies of diabetic women the birth weights of the infants are significantly smaller and the fetal as well as maternal complication-rates significantly higher than in those of women without nephropathy. Also 3 years after delivery, the body weight of the children of nephropathic diabetic women is significantly lower than that of children of diabetic women without nephropathy. Additionally, children of nephropathic women are retarded in terms of linguistic development and their resistance to infections is reduced.

[Cerebrolysin in treatment of painful diabetic neuropathy]. / Cerebrolysin in der Behandlung der schmerzhaften diabetischen Neuropathie.

Cerebrolysin is a peptide solution with free amino acids and biologically active peptides showing neurotrophic efficiency. In a placebo-controlled longitudinal study we investigated the effect of that drug for treatment of painful diabetic neuropathy in 20 type-II diabetic patients (9 women, 11 men, mean age 63 +/- 9 years, duration of diabetes 14 +/- 7 years). Patients received daily a cerebrolysin-infusion (20 ml in 500 ml Ringer) over a period of 10 days. In an age- and diabetes-duration matched placebo group of 10 type-II diabetic patients (7 women, 3 men, age 66 +/- 9 years, duration of diabetes 12 +/- 5 years) vitamin B infusion was administered (5 ml vitamin B complex in 500 ml Ringer) during 10 days. We compared a five-item symptom score scale (FIS) for pain, dysesthesia, paresthesia, nightly exacerbation, and sleep disturbances (grade 0 to 3) and a graphic visual analogue rating scale (VAS) for recording the magnitude of the pains (scale 0 to 100 mm) at the beginning and the end of the infusion therapy as well as 6 weeks later. Cerebrolysin was associated with a significant decrease in total FIS score from 8.7 +/- 1.9 at the start of therapy to 5.1 +/- 2.2 after 6 weeks (p < 0.001), and to a reduction of the VAS score from 4.2 +/- 0.8 to 2.8 +/- 0.9 (p < 0.001) during the same period of observation. In contrast in the placebo group the total FIS score decreased only from 7.9 +/- 1.2 at the beginning to 6.6 +/- 1.1 (p < 0.05) 6 weeks later and the VAS score from 4.5 +/- 0.6 to 4.0 +/- 0.5 (NS). Thus cerebrolysin led to a significant subjective improvement of painful diabetic neuropathy in type-II diabetic patients at least for a period of 6 weeks.

[Risk for hyperkalemia during long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetics in relation to the glomerular filtration rate]. / Hyperkaliämierisiko unter Langzeittherapie mit ACE-Hemmern bei insulinpflichtigen Typ-2-Diabetikern in Abhängigkeit von der GFR.

BACKGROUND AND OBJECTIVE: The risk for hyperkalaemia during therapy with angiotensin-converting enzyme inhibitors is especially increased in the elderly diabetic because of a decrease in glomerular filtration rate (GFR), as well as the occurrence of hyporeninaemic hypoaldosteronism. We evaluated the risk for hyperkalaemia under long-term angiotensin-converting enyzme inhibition in 86 insulin-dependent type 2 diabetic patients in relation to their GFR. PATIENTS AND METHODS: We compared the influence of a 3 to 6 months long treatment with angiotensin-converting enzyme inhibitors on the serum potassium levels, the creatinine clearance and the urinary albumin excretion in insulin-dependent type 2 diabetic patients with an initial creatinine clearance < 50 ml/min/1.73m(2) (n = 15, age 66 +/- 6 years) and >/= 50 ml/min/1.73m(2) respectively (n = 71, age 61 +/- 10 years). In addition, we also investigated the influence on the metabolic control and the blood pressure values in both groups of patients. RESULTS: In the patients with creatinine clearance >/= 50 ml/min/1,73m(2) the mean potassium level increased from 4.3 +/- 0.2 to 4.6 +/- 0.4 mmol/l (P < 0,01), while the incidence of a potassium level > 5 mmol/l was 17 %. In the group with a creatinine clearance < 50 ml/min/1.73m(2) the potassium level rose from 4.5 +/- 0.2 to 5.0 +/- 0.4 mmol/l (P < 0.01). The incidence of potassium levels > 5 mmol/l was 66 % (P < 0,01). In both patient groups the creatinine clearances did not change significantly during angiotensin-converting enzyme inhibition, and the urinary albumin excretion as well as the HbA(1c) values and blood pressure showed only a tendency towards a decrease. CONCLUSION: Long-term treatment with angiotensin-converting enzyme inhibitors in insulin-dependent type 2 diabetic patients leads to a significant increase in serum potassium. The incidence of hyperkalaemia with potassium levels > 5 mmol/l is significantly higher in the patients with initial creatinine clearance < 50 ml/min/1.73m(2). Severe hyperkalaemia with potassium levels > 6 mmol/l was not observed.

[Successful outcome of high-risk pregnancy within 1 year following kidney transplantation with cyclosporin as the immunosuppressive agent]. / Erfolgreiche Risikoschwangerschaft im 1. Jahr nach Nierentransplantation mit Cyclosporin als Immunsuppressivum.

A 41-year-old female patient with analgesic nephropathy became pregnant 13 weeks after successful renal transplantation using cyclosporin as an immunosuppressant. Because of rhesus incompatibility of the mother this was thought to be a high risk pregnancy. In spite of the increased risk of CyA-induced nephrotoxicity in this early phase after transplantation, the patient showed the same physiological renal changes during pregnancy as healthy control patients: a 24% increase in creatinine clearance and an increase in protein excretion of only 41 mg/day. To maintain a CyA-blood concentration of 200-600 ng/ml throughout the pregnancy the CyA dose had to be increased from 380 to 550 mg daily or from 6.9 to 8.3 mg/kg/day (20%). This increase in CyA requirement may indicate additional metabolism of CyA by the fetal liver.

[The lipid lowering effect of a new guar-pectin fiber mixture in type II diabetic patients with hypercholesterolemia]. / Lipid-senkender Effekt eines neuen Guar-Pektin-Ballaststoffgemisches bei Typ II-Diabetikerinnen mit Hypercholesterinämie.

The lipid-lowering effect of a new mixture of fiber consisting in guar and apple-pectin in combination with apple-pomaces has been estimated in 15 female type 2-diabetics [age mean = 62 (52-70) yr] with hypercholesterolemia (total-chol > 240 mg/dl and LDL-chol > 130 mg/dl). After a dietetic run-in-phase of 3 weeks the patients received the fiber mixture (1 package of 17 g with about 5.9 g water-soluble fiber) dissolved in 250 ml water for the next 9 weeks: during the first 3 weeks 2 portions per day, the next 3 weeks twice 1/2 portion and the last 3 weeks one 1/2 portion daily. The fiber mixture had to been consumed 30 minutes before taking a main meal. Regular intake of the fiber product led to a significant decrement in blood lipids, and this improvement under 2 portions daily has been maintained for the most part with the reduced dosage. The total-chol levels decreased by 11.3% during the first 3 weeks of fiber intake (p < 0.05) and by -12.6% during the next 3 weeks (p < 0.05), the decrease during the last 3 weeks under the reduced fiber intake was -9.6% (ns). The HDL-chol levels remained approximately the same during the whole period of observation. The triglyceride concentrations in serum could be lowered by -15.5% during the first 3 weeks of fiber intake, and by -19.2% during the next 3 weeks (p < 0.05), finally the decrease was -12.3% (ns). The atherogenic index (Chol-/HDL-chol) could be reduced on an average of 14.3% in relation to the initial value.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement in prognosis of patients with acute renal failure over a period of 15 years: an analysis of 710 cases in a dialysis center.

In order to evaluate the changes in causes and outcome of acute renal failure (ARF) during the years 1975-1989, 710 patients treated in our dialysis center were analyzed. We compared the etiology, the severity and catabolic state of ARF, the techniques of renal replacement therapy, which were employed and the ages and mortality rates of these patients, who received dialysis therapy during the years 1975-79 (n = 227), 1980-84 (n = 240) and 1985-89 (n = 243). The number of postoperative, posttraumatic and non-traumatic cases of ARF was approximately the same in all three 5-year periods, only the frequency of postrenal failure decreased from 7% in the years 1975-79 to 3% in the years 1985-89. The incidence of sepsis as a major cause of ARF and the most important risk factor was comparably high in the surgical and medical patients during all of the periods, but it increased in the traumatic patients from 7% in the years 1975-79 to 28% during the last 5-year period. The prevalence of respiratory failure and jaundice as additional organ failures, the severity of ARF (oligonanuric-nonoliguric) and the metabolic state were not different in the three patient groups. The magnitude of rise in serum creatinine before the start of renal replacement therapy was significant lower in the last 5-year period in comparison to the years 1975-79 (p < 0.05). Hemodialysis was the treatment in choice of 98 and 93% of the cases during the first two periods, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Microalbuminuria in essential hypertension and normal kidney function]. / Mikroalbuminurie bei essentieller Hypertonie und normaler Nierenfunktion.

In patients with essential hypertension increased albumin excretion in the urine compared to healthy controls is well known. In 38 patients (age: Mean +/- SD = 37 +/- 16 yr, f: m = 19:19) with benign essential hypertension and normal renal function (creatinine clearance: Mean +/- SD = 99 +/- 16 ml/min) we found a mean urinary albumin excretion of 79 +/- 61 mg/24 h in comparison to 14 +/- 13 mg/24 h (p less than 0.01) in 10 healthy controls (age: Mean +/- SD = 35 +/- 14 yr, f: m = 5:5). In 13 patients with hypertension urinary albumin excretion was increased (greater than 25 mg/24 h) in a subclinical range (microalbuminuria), the other 25 hypertensive patients had normoalbuminuria. Comparing the hypertensive patients with and without microalbuminuria, those with elevated albumin excretion were older (age: Mean +/- SD = 42 +/- 12 yr vs. 32 +/- 19 yr), had a longer average duration of hypertension (8 +/- 5 yr vs. 5 +/- 4 yr) and a higher prevalence both of hypertensive retinopathy (77% vs. 28%) and of abnormalities in the electrocardiogram (23% vs. 4%) than those with normal albumin excretion. The difference in the prevalence of hypertensive retinopathy (grade I and II) was statistically significant (p less than 0.05). Furthermore the patients with microalbuminuria required a more intensive antihypertensive therapy than those with normoalbuminuria, 46% requiring triple drug therapy as opposed to 24% in the latter group. Thus the demonstration of microalbuminuria in patients with benign essential hypertension is associated with a higher prevalence of funduscopic and electrocardiographic abnormalities, and therefore can be considered as an indicator of early vascular damage in essential hypertension.

[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).

[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.

Human adjuvant disease: remission of silicone induced autoimmune disease after explanation of breast augmentation.

Autoimmune diseases following silicone or paraffin implantation are rarely encountered complications of plastic surgery. A 42 year old woman is presented who developed clinical and immunological features of systemic lupus erythematosus 11 years after silicone augmentation. After explanation antinuclear antibody titres decreased from 1/1280 to 1/160, C4 complement fraction and the previously raised angiotensin converting enzyme normalised in step with clinical improvement. It is important that plastic surgeons and rheumatologists should be aware of this possible association.

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)

Severe tubulopathy and kidney graft rupture after coadministration of mannitol and ciclosporin.

Spontaneous allograft rupture after kidney transplantation is a rare complication usually due to an acute rejection of the interstitial type. In a 32-year-old man kidney transplantation was performed under immunosuppression with prednisolone and ciclosporin (CS). The dose of CS was 5 mg/kg body weight intravenously for the first 24 h, on the 2nd day 10 mg/kg/day orally, with gradually decreasing doses thereafter. The patient remained oliguric in the postoperative period and received additionally 600 ml mannitol solution intravenously for osmodiuresis within a period of 6 days. On the 8th postoperative day, 48 h after the last intravenous infusion of mannitol, spontaneous renal rupture occurred. The CS concentrations in the blood during the days before the rupture were within the upper normal range for effective immunosuppression (300-600 ng/ml). Intraoperatively the kidney appeared enlarged due to edematous swelling of the graft, but it showed no signs of rejection. The histological finding was a toxic tubulopathy with extensive isometric vacuolization and peritubular congestion, a known side effect of both of CS and of mannitol. The rupture was successfully repaired. Thirty-four days after the transplantation diuresis increased and hemodialysis therapy could be discontinued. In a second biopsy of the kidney the signs of toxic tubulopathy with isometric vacuolization were reduced. On the following days the serum creatinine dropped below 160 mumol/l. It can be assumed that the combination of CS therapy and administration of massive and continued doses of mannitol in an oliguric patient with allograft kidney may potentiate severe tubulopathy with concomitant edematous swelling of the graft. This can result in an increasing danger of spontaneous renal rupture.