Christine K. Keller

Increased prevalence of salt sensitivity of blood pressure in IDDM with and without microalbuminuria

SummaryIn insulin-dependent diabetes mellitus (IDDM) elevated exchangeable sodium (Na) levels are found even in the absence of hypertension, but it is not known whether this is associated with increased sensitivity of blood pressure to sodium level. To clarify this issue we compared 30 patients with IDDM (19 without and 11 with microalbuminuria, i.e. more than 30 mg albumin/day) and 30 control subjects matched for age, gender and body mass index. The subjects were studied on the 4th day of a low-salt diet (20 mmol/day) under in-patient conditions and were subsequently changed to the same diet with a high-salt supplement, yielding a total daily intake of 220 mmol Na/day. Circadian blood pressure, plasma renin activity (PRA), plasma atrial natriuretic factor (p-ANF), plasma cyclic guanosine 5′-phosphate (p-cGMP) and urinary albumin were measured. The proportion of salt-sensitive subjects, i.e. showing increment of mean arterial pressure ≥ 3 mmHg on high-salt diet, was 43% in diabetic patients (50% of diabetic patients with and 37% without microalbuminuria) and 17% in control subjects (p<0.05). Lying and standing PRA levels on low- or high-salt diet were significantly lower in diabetic patients than in control subjects. Salt-sensitive diabetic patients had significantly higher lying ANF on high-salt (38.7±4.2 pmol/l vs 20.1±2.3 pmol/l, p<0.005) than on low-salt diet. The results suggest that (i) the prevalence of sodium sensitivity is high in IDDM (ii) sodium sensitivity is found even in the absence of nephropathy as indicated by albuminuria.

Pathogenesis and course of renal disease in IDDM/NIDDM: differences and similarities.

In the past the opinion prevailed that renal prognosis was less adverse in non-insulin-dependent diabetes mellitus (NIDDM) as compared with insulin-dependent diabetes mellitus (IDDM). This notion has to be revised in the light of recent evidence, based on epidemiologic data of NIDDM patients reaching endstage renal failure and a comparison of the cumulative prevalence of proteinuria and renal failure, respectively, in NIDDM as compared with IDDM. It has also been established that initial renal hemodynamic changes are quite comparable in NIDDM and in IDDM. It follows that past complacency about the renal sequelae of NIDDM is no longer justified and that preventive measures to interfere with the development of diabetic nephropathy are similarly important in NIDDM and IDDM.

Altered action of angiotensin II in patients with type 2 diabetes mellitus of recent onset.

Objective Angiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity. Design and methods Twelve healthy volunteers (aged 43 ± 9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45 ± 9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) and p-aminohippurate (CPAH) clearance methods, respectively. Results In volunteers the mean M-value after Ang II infusion (10.1 ± 1.5 mg/kg per min) was significantly higher (P < 0.01) than that after sham infusion (8.2 ± 0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1 ± 1.3 mg/kg per min) and sham infusion (5.5 ± 1.2 mg/kg per min). The difference in the mean absolute increase in the M value (ΔM) between groups was significant (P < 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0 ± 3.5 to 15.5 ± 3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8 ± 3.3 to 19.1 ± 3.7 ml/100 ml per min, P < 0.01). Again, the difference between the mean absolute increases in MBF (ΔMBF) in the groups was significant (P < 0.01). A significant correlation was found between ΔMBF and ΔM (r = 0.62, P < 0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAH and fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients. Conclusions In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.

Renal involvement in type II diabetes

The incidence and prevalence of renal failure from type II diabetes have been seriously underestimated in the past. Currently, the incidence of uremia in patients with type II diabetes has increased continuously in Europe and the United States, mainly because of better patient survival (ie, they now live until nephropathy develops) and possibly because of a rising prevalence of type II diabetes in the general population (ie, more patients are at risk of developing nephropathy). Generally, renal hemodynamics and glomerular lesions are similar in type I and type II diabetes, but glomerular histology is more diverse in type II diabetes. Given the high prevalence of diabetes and renal failure from various causes in the elderly, coexistence of the two (even in the absence of glomerulosclerosis) occurs in approximately 20% of uremic type II diabetic patients. The development of nephropathy is controlled by strong genetic determinants, but these have not been further characterized.

Nephropathie und Hypertonie bei Typ-II-Diabetes

Zusammenfassung□ HintergrundDie Nephropathie des Typ-II-Diabetikers ist heute in Deutschland die häufigste Ursache einer der Nierenersatztherapie bedürftigen terminalen Niereninsuffizienz. Vor diesem Hintergrund kommt präventiven Maßnahmen große Bedeutung zu.□ Diabetische Nephropathie und HypertonieBei etablierter diabetischer Nephropathie ist die Hypertonie der wichtigste therapeutisch angehbare pathogenetische Faktor. Es werden daher einige für die Durchführung der antihypertensiven Therapie wichtige pathogenetischen Zusammenhänge dargestellt und die Beziehung zwischen Hypertonie und diabetischer Nephropathie analysiert.□ SchlußfolgerungDiabetische Nephropathie bei Typ-II-Diabetes ist derzeit die häufigste Ursache einer terminalen Niereninsuffizienz in Deutschland. Präventive Maßnahmen (normale Blutzuckereinstellung, vor allem jedoch antihypertensive Therapie) haben einen gesicherten hemmenden Effekt auf das Fortschreiten der Niereninsuffizienz bei diabetischer Nephropathie. Zur Früherkennung der diabetischen Nephropathie ist der Urinalbuminnachweis (Mikroalbuminurie) geeignet. Bei Patienten mit diabetischer Nephropathie ist die Senkung des Blutdrucks durch diätetische Kochsalzbeschränkung und medikamentöse antihypertensive Therapie in den mittleren normotensiven Bereich dringend indiziert.Summary□ BackgroundIn Germany nephropathy in patients with type II diabetes has become the most frequent single cause of uremia requiring renal replacement therapy. This calls for effective measures of prevention□ Diabetic Nephropathy and HypertensionIn patients with established diabetic nephropathy, hypertension is the most important pathogenetic factor which is susceptible to therapeutic intervention. Some pathogenetic mechanisms are discussed which impact on antihypertensive therapy. Interaction between hypertension and diabetic nephropathy is analyzed.□ ConclusionDiabetic nephropathy in patients with type II diabetes has become the most frequent cause of endstage renal failure in Germany. Preventive measures, i. e. near normal glycemia and particularly antihypertensive treatment, have been proven to interfere with progression of renal failure in diabetic nephropathy. Early recognition is possible by testing for urinary albumin (microalbuminuria). In patients with diabetic nephropathy, blood pressure should be lowered to values well within the range of normotension by dietary salt restriction and antihypertensive drug therapy.

Pharmakotherapie bei Niereninsuffizienz

Die pharmakokinetischen Eigenschaften von Medikamenten konnen bei eingeschrankter Nierenfunktion verandert sein. Bei Nieren- oder Leberfunktionsstorung, aber auch bei alteren Menschen, liegt haufig ein veranderter Arzneimittelmetabolismus vor.

Nephrologische Begutachtung und arbeitsmedizinische Aspekte bei chronischer Niereninsuffizienz

Die Erstellung von Gutachten gehort zu den sozialoffentlichen Aufgaben des Arztes. Speziell chronische Erkrankungen verlangen eine besondere Beachtung der Beeintrachtigung der Lebensqualitat in der gutachterlichen Stellungnahme.

Tubulointerstitielle Erkrankungen der Niere

Eine Schadigung des tubulointerstitiellen Gewebes begleitet fast jede chronische Nierenerkrankung. Dies ist unabhangig von der ursprunglich betroffenen anatomischen Struktur (Glomeruli, Gefase, Nierenbecken). Das Ausmas der tubulointerstitiellen Schadigung korreliert mit der Progression der Niereninsuffizienz besser als das Ausmas der glomerularen Schaden.

Raumforderungen in der Niere

Die haufigste Raumforderung in der Niere ist die einfache Nierenzyste, die meist 2,5–3 cm (Bereich 0,5–10 cm) Durchmesser aufweist (Abb. 6–1). Sie ist in der Regel ein sonographischer Zufallsbefund, der mit zunehmenden Alter haufiger auftritt. Manner sind mehr als doppelt so oft betroffen. Beidseitige oder multiple einfache Zysten sind besonders bei jungen Personen selten, eine Zysteninfektion einer Solitarzyste ist eine Raritat. Letztere kann bei Persistenz eine chirurgische Sanierung mittels Drainage oder Resektion erfordern. Haufiger als Infektionen von Solitarzysten ist eine durch eine beachtliche Grose hervorgerufene, schmerzhafte Kapselspannung. Sie kann chirurgisch entlastet werden. Open image in new window

Fehlbildungen und erbliche Nierenerkrankungen

Angeborene Anomalien der Niere oder der ableitenden Harnwege bilden etwa 20% der pranatalen Fehlbildungen. Man unterscheidet Agenesien, Hypoplasien, Doppelanlagen, Lageanomalien und zystische Fehlbildungen. Eine haufige Fehlbildung ist die Doppelanlage der Niere mit unvollstandiger Trennung der Nierenbecken, sonographisch als Parenchymbrucke erkennbar. Viele erbliche Nierenerkrankungen manifestieren sich bereits in der fruhen Kindheit. Man unterscheidet zystische, glomerulare und tubulare Formen sowie Stoffwechselerkrankungen mit Nierenbeteiligung. Mit einer Haufigkeit von 1/400–1000 ist die autosomal dominante polyzystische Nierenerkrankung die haufigste erbliche Nierenerkrankung. Im mittleren bis hoheren Lebensalter fuhrt sie zu Hypertonie und Niereninsuffizienz.