[Treatment of renal artery stenosis in the year 2021]. / Behandlung der Nierenarterienstenose im Jahr 2021.

Severe arteriosclerotic stenosis of the renal artery with at least 60-70% narrowing of the lumen can lead to various diseases: in the case of unilateral stenosis it can lead to renovascular hypertension, in the case of bilateral narrowing (or in a stenotic solitary kidney) also to an often progressive renal insufficiency (ischemic kidney disease) and/or to acute pulmonary edema (pulmonary flash edema). Renal artery stenosis may be treated by revascularization using either percutaneous (balloon angioplasty with or without stenting) or less commonly open surgical procedures, both with excellent primary patency rates of over 90%; however, randomized trials of catheter-based interventions have failed to demonstrate a longer term benefit with respect to blood pressure control and renal function as well as improved overall survival over optimal medicinal management alone. Due to improved clinical outcomes interventional revascularization is justified in cases with critical stenoses and clinical sequelae, such as pulmonary flash edema and progressive renal failure. Careful patient selection is essential to maximize a potential clinical benefit.

Current management of renal artery stenosis.

Severe renal artery stenosis may cause renovascular hypertension; in case of bilateral narrowing or in a stenotic solitary kidney, renal insufficiency (e.g. ischemic kidney disease) or pulmonary flash edema may ensue. Renal artery stenosis can be treated by revasularization, using either percutaneous angioplasty (with or without stenting) or less common open surgical procedures, both with excellent primary patency rates. However, several randomized trials of renal artery angioplasty or stenting in patients with arteriosclerotic disease have failed to demonstrate a longer-term benefit with regard to blood pressure control and renal function over medical management. It has not yet been demonstrated that renal revascularization leads to a prolongation of event-free survival. Furthermore, endovascular procedures are associated with substantial risks. If revascularization is envisaged careful patient selection, e.g. patients with refractory hypertension or progressive renal failure, is important to maximize the potential benefit.

Multicenter study on the diagnostic value of a new RIA for the detection of free plasma metanephrines in the work-up for pheochromocytoma.

Available laboratory test methods for the detection of elevated concentrations of catecholamines and their metabolites in urine and/or plasma are not always sensitive enough for the detection of pheochromocytoma. High-quality immunoassays for these compounds appear to be as accurate as high-pressure liquid chromatography (HPLC) or gas chromatography/mass spectrometry (GC-MS). Therefore, the current project aims to establish a new sensitive radioimmunoassay (RIA) for the measurement of free metanephrines in the plasma of patients in the work-up for pheochromocytoma. We report first results of an ongoing multicenter clinico-chemical evaluation study in hypertensive patients and normotensive volunteers. After an overnight fast plasma samples were collected on ice in EDTA- and heparin-coated tubes after insertion of an indwelling venous line and resting in the supine (patients) or sitting position (normal volunteers) for 30 min. Plasma metanephrines were measured by a newly developed RIA from IBL, Hamburg, Germany. Good agreement of the assay with the tandem mass spectrometry (LC-MS/MS) method for normetanephrine (r2=0.975) and for metanephrine (r2=0.985) could be demonstrated. Both specimens, EDTA and heparin plasma, can be used with the same results. The RIA has a good precision of <15% in the normal range and of <10% in the elevated concentration range. Our preliminary data suggest a high validity of the newly developed RIA for measuring free metanephrine and normetanephrine in hypertensive subjects in both EDTA and heparin plasma. Further work is required to determine the accuracy of the test in larger patient populations and in patients with pheochromocytoma.

Proteinuria in diabetic patients--is it always diabetic nephropathy?

BACKGROUND: Diabetic nephropathy (dNP) is a consequence of type 1 and type 2 diabetes, typically occurring between 5 and 15 years after diabetes has been diagnosed. The coincidence of dNP and diabetic retinopathy (dRP) is well known. In this study we correlated the histological findings of the kidney biopsy with the clinically expected diagnosis of dNP. PATIENTS AND METHODS: Over a 4-year period with a total of 326 kidney biopsies, 85 biopsies were performed on patients with diabetes. In all of these patients we had information about duration of diabetes and ophthalmological status. Additionally, data about proteinuria, urine sediment and autoantibodies were available. The nephrologist had to give the suspected diagnosis before the biopsy was performed, using the clinical data available. RESULTS: In 57 patients (67%) dNP was predicted clinically before biopsy. In 28 patients we expected a different kind of kidney disease. Only 43 patients had dNP histologically. In 16 out of 19 patients with dRP we also found dNP. 26 patients with dNP did not have dRP. So dRP was very specific but not sensitive to predict dNP. On the other hand, all patients without dRP but acanthocytes in urine sediment had non-diabetic kidney disease (NDKD). In the case of patients with neither dRP nor acanthocytes, it was very difficult to distinguish between dNP and NDKD. Acanthocytes and antineutrophil cytoplasmatic antibodies with positive antibodies for proteinase 3 or myeloperoxidase were found only in NDKD, but ANAs were detected in a wide titer range in dNP and NDKD. The known duration of the diabetes ranged from 1 to 40 years. There were no additional parameters to differentiate this group. CONCLUSIONS: Diabetic patients with dRP and proteinuria frequently have dNP. In patients without typical retinal findings dNP is less likely, thus a kidney biopsy is necessary to confirm the diagnosis. Additional knowledge about urine sediment and autoantibodies is helpful, but is not sufficient to differentiate NDKD from dNP in the majority of patients.

Vascular endothelial growth factor and its soluble receptor, Flt-1, are not correlated to erythropoietin in diabetics with normal or reduced renal function.

BACKGROUND AND AIMS: Recombinant erythropoietin upregulates the expression of the vascular endothelial growth factor (VEGF) receptors, Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), in endothelial cells. The integrity of the VEGF system seems to be crucial for the regulation of endothelial permeability and thus for the avoidance of renal protein leakage. As albuminuria/proteinuria is a hallmark of diabetic nephropathy, we examined cross-sectionally in 35 type 1 and 37 type 2 diabetic patients with various degrees of renal dysfunction and albuminuria whether there was an interrelationship between intrinsic erythropoietin (EPO) and VEGF/Flt-1. METHODS AND RESULTS: In patients with plasma creatinine values < or =1.5 (n = 53) or >1.5 mg/dL (n = 19), the mean serum EPO was 5.6 +/- 4.4 and 10.2 +/- 7.0 mU/mL (P = 0.02), respectively. In the two groups, urinary and serum VEGF(165) concentrations were similarly distributed (mean 94.3 +/- 91.8 vs 108 +/- 72.2 ng/L and 91.7 +/- 76.8 vs 91.9 +/- 74.9 ng/L, respectively; both P = NS). The mean urinary Flt-1 for the two groups amounted to 0.14 +/- 0.35 and 0.51 +/- 0.93 ng/mL (P = 0.045), respectively. No correlation between VEGF or Flt-1 and EPO was apparent. CONCLUSION: Our data suggest that in vivo EPO does not affect the functionality and/or production of components of the VEGF/Flt-1 system in diabetics with normal or reduced renal function.

[Potassium in renal disease]. / Nierenerkrankungen: cave Kalium!

BACKGROUND: Hypokalemia and hyperkalemia are among the most common disturbances of the electrolyte status. PATIENTS AND RESULTS: Since the regulation of the potassium homeostasis depends on normal renal function, patients with acute or chronic renal disease tend to develop such disturbances. The clinical consequences of hypokalemia or hyperkalemia are often severe and unforeseen, which is illustrated by respective case reports in this paper. CONCLUSION: Due to the often severe clinical consequences of hypokalemia or hyperkalemia, these electrolyte disturbances deserve special diagnostic and therapeutic attention.

Vascular endothelial growth factor in diabetic nephropathy.

BACKGROUND: Vascular endothelial growth factor (VEGF) increases endothelial permeability. VEGF is produced in podocytes and functional receptors are located on endothelial glomerular cells. The aim of the current study in diabetic patients with normal renal function to various degrees of proteinuric nephropathy was therefore to unravel a possible role of the most important isoform VEGF(165) for albuminuria and to investigate the impact of therapy with an inhibitor of the renin-angiotensin system on VEGF(165) secretion. SUBJECTS AND METHODS: A cross-sectional study in 72 patients (41 female, 31 male) with long-standing type 1 (n = 35, mean age 43.3 years, range 22-67) or type 2 (n = 37, mean age 66 years, range 53-83) diabetes mellitus was performed; in 19 patients the serum creatinine value was >1.5 mg/dl. Twenty-six healthy volunteers (17 female, 9 male, mean age 34.8 years, range 19-58) with normal renal function served as controls. Serum and urinary VEGF(165) was measured by ELISA. Urinary albumin was measured nephelometrically. Mann Whitney U tests were used for comparisons. RESULTS: In type 1 and type 2 diabetics mean urinary VEGF(165) concentration amounted to 112 +/- 88 (mean +/- SD) and 88 +/- 85 ng/l, respectively, compared to 101 +/- 60 ng/l in the normal volunteers (NS vs. diabetics). The respective mean urinary albumin concentrations were 443 +/- 1029, 394 +/- 749 and 20 +/- 33 mg/l (p < 0.01 vs. diabetics type 2). There was a correlation between urinary VEGF and albumin, but only in patients with type 2 diabetes (R = 0.497; n = 36; p = 0.002). Urinary VEGF(165) was similar in patients with (n = 40) and without ACE inhibitor/AT1 antagonist therapy (n = 32) and in normal volunteers, whereas serum VEGF(165) was higher in the treated type 1 diabetics. CONCLUSIONS: These results may suggest that VEGF(165) plays some role in the development of albuminuria in diabetic nephropathy due to type 2 but not type 1 diabetes.

Immunosuppressive therapy regimen and platelet activation in renal transplant patients.

BACKGROUND: Increased platelet activation caused by an immunosuppressive therapy regimen may contribute to the high incidence of death from cardiovascular disease in renal transplant patients. Cyclosporine (INN, ciclosporin) and azathioprine are reported to activate platelets, but data are rare and controversial for tacrolimus and mycophenolate mofetil. METHODS: This cross-sectional study assessed markers of platelet degranulation (P-selectin; CD62), the activated glycoprotein IIb/IIIa receptor (PAC1, indicating the fibrinogen binding site), platelet aggregation, and secretion of platelet-derived growth factor (PDGF(AB)) in renal transplant patients treated with 4 different therapy regimens. Immunosuppression was based on low-dose steroids (5 mg/d prednisone) in combination with a single agent: (1) cyclosporine (n = 16), (2) azathioprine (n = 18), (3) tacrolimus (n = 17), or (4) mycophenolate mofetil (n = 13). Effects were compared with those in an age-matched control group of patients with hypertension (n = 11). RESULTS: In all renal transplant patient groups, unactivated platelets exhibited an increased expression of CD62. When stimulated with 2-micromol/L thrombin receptor-activating peptide, CD62 expression in platelets from patients treated with azathioprine (63% +/- 17%; P <.05), cyclosporine (51% +/- 23%; P <.05), and tacrolimus (50% +/- 22%; P <.05) was elevated compared with control subjects (33% +/- 19%). PAC1 expression was significantly increased in the patient groups that received azathioprine and cyclosporine. PDGF(AB) secretion was elevated in patients treated with azathioprine only (51 +/- 24 ng/10(9) platelets [versus 35 +/- 17 ng/10(9) platelets for control subjects]; P <.05). Platelet aggregation in response to collagen (0.5 microg/mL) was decreased in patients treated with tacrolimus (49% +/- 29%; P <.05) and mycophenolate mofetil (55% +/- 32%; P <.05) compared with control subjects (73% +/- 25%). CONCLUSION: This is the first study to compare the effects on platelet function of different immunosuppressive regimens that are based on monotherapy. All renal transplant patients showed preactivated platelets compared with those of patients with hypertension. However, the "newer" immunosuppressive agents tacrolimus and mycophenolate mofetil seemed to have fewer unfavorable effects on platelet CD62 expression and PAC1 expression and aggregation. Whether this finding is accompanied by fewer cardiovascular events remains to be elucidated.

Diagnosis of pheochromocytoma.

The purpose of this article is to give an overview on recent advances in the diagnosis, localization by imaging and treatment of pheochromocytoma. Pheochromocytoma is a mostly benign tumor (malignancy rate 10-15%) which arises from chromaffin cells with excessive catecholamine production and secretion. Most tumors are localized in the adrenals but 15-18% of the lesions are found extraadrenally (paragangliomas). Pheochromocytoma is a rare form of secondary hypertension; it can also be found as a feature of familial disease (e.g. von Hippel-Lindau disease, MEN type II) due to genetic mutations of several genes that have been identified recently. In familial pheochromocytoma molecular genetic analysis has improved the diagnostic modalities. In such patients the tumor can occur bilaterally and patients often remain normotensive until the tumor produces sufficient catecholamines to have hemodynamic effects. The extreme importance of recognizing this tumor is evident from the fact that it can be successfully removed in about 90% of the cases, whereas if unrecognized the tumor poses great risk of death or devastating complications. Diagnostic screening includes measurement of catecholamines and their metabolites (metanephrines) in plasma and/or urine. Furthermore, pharmacological testing (e.g. clonidine suppression test) may be indicated in patients with moderately elevated catecholamines or when the diagnosis is still uncertain. Several imaging techniques are applied to localize the tumor. Abdominal CT scan is still considered the "gold standard" since about 98% of the tumors lie infradiaphragmatically. Magnetic resonance imaging (MRI) and MIBG-scanning are other useful methods. Recently, positron emission tomography (PET) based techniques have also been developed. After the diagnosis is made tumor removal following pharmacological pretreatment is the decisive therapeutic measure.